Lupus 2014 Abstracts 449 99

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Innate and adaptive immunity

Lupus 2014 23: 449
DOI: 10.1177/0961203314527038
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ABSTRACTS
9th European Lupus Meeting,

April 2326 2014, Athens, Greece
Innate and adaptive immunity
A002
A001
ANALYSIS OF CIRCULATING INTERFERON LEVELS IN

LUPUS PATIENTS FROM MULTIPLE WORLD POPULATIONS
REVEALS LOW IFN-A IN PATIENTS FROM THE ISLAND
POPULATION OF CRETE
Chrabot B.S.1, Zervou M.I.2, Jolly M.3, Boumpas D.T.4,5,6,
Goulielmos G.N.2 and Niewold T.B.7
1
Section of Rheumatology and Gwen Knapp Center for Lupus and
Immunology Research, University of Chicago, IL, USA 2Molecular
Medicine and Human Genetics Section, Medical School of Crete,
Heraklion, Greece 3Division of Rheumatology and Rush Lupus Clinic,
Rush University Medical Center, Chicago, IL, USA 4Institute of
Molecular Biology and Biotechnology, FORTH-Hellas, Voutes,
Heraklion, Greece 5Biomedical Research Foundation, Academy of
Athens, Greece 6Faculty of Medicine, National and Kapodestrian
University of Athens, Athens, Greece 7Division of Rheumatology,
Department of Immunology, Mayo Clinic, Rochester, MN, USA
ACTIVATED T CELLS ENHANCE THE INTERFERON-a

PRODUCTION BY RNA-IC STIMULATED PLASMACYTOID
DENDRITIC CELLS
Leonard D.1, Eloranta M-L.1, Hagberg N.1, Berggren O.1, Tandre K.1,
Alm G.2 and Ronnblom L.1
1
Department of Medical Sciences, Rheumatology, Uppsala University,
Uppsala, Sweden. 2Department of Biomedical Sciences and Veterinary
Public Health, Swedish University of Agricultural Sciences, Uppsala,
Sweden
Introduction: A prominent interferon-a (IFNa) signature is seen in several
autoimmune diseases, including systemic lupus erythematosus (SLE).
Aim: We asked if T cells can promote the IFNa production by plasmacytoid dendritic cells (pDCs) stimulated with RNA containing
immune complexes.
Patients and Methods: Human T cells were activated by anti-CD3/
CD28 antibodies or in a mixed leukocyte reaction (MLR). T cells or
supernatant from T cell cultures were co-cultured with pDCs stimulated with immune complexes containing U1 snRNP particles and
SLE-IgG (RNA-IC). Cells were analyzed by flow cytometry and cytokines in co-culture supernatants were depleted or blocked by monoclonal antibodies. Culture supernatants were analyzed after 20h for IFNa
and other cytokines.
Results: Activated T cells or supernatants from activated T cells
increased the IFNa production >20-fold. After addition of cytokines
to RNA-IC stimulated pDCs, GM-CSF and IL-3 was demonstrated to
increase the IFNa production. This stimulatory effect was reduced
after depletion of GM-CSF in supernatants from activated T cells
(81%), blocking of GM-CSF (78%) or its receptor subunits CD131
and CD116 (70-75%). Supernatant from activated T cells also
increased the frequency of CD80 and CD86 expressing RNA-IC stimulated pDC from 7% to 37% and 8% to 21%, respectively.
Activated SLE-T cells enhanced the IFNa production in RNA-IC
stimulated pDC to the same extent as activated T cells from healthy
individuals. Elevated levels of serum-GM-CSF (4.2-128 pg/ml) was
found in 30% of SLE patients, all characterized by increased levels
of serum-IFNa (3.0-29 U/ml)
Conclusion: Activated T cells enhance the IFNa production by RNAIC stimulated pDCs via GM-CSF and IL-3 and induces maturation of
the pDCs. The observation that all SLE patients with measurable
serum levels of GM-CSF had elevated serum levels of IFNa indicates
that activated T cells may be important for the ongoing IFNa production in this disease.
Introduction: Interferon alpha (IFN-a) is a primary pathogenic factor

in systemic lupus erythematosus (SLE). Levels of IFN-a may differ
between SLE patients from different ancestral backgrounds, and this
information could be important as therapeutics are developed that
target this pathway.
Aim: In this study, we compare circulating IFN-a levels in SLE patients
from different world populations.
Patients and Methods: 364 SLE patients were included in the study: 129
African-American, 134 European-American, 41 Hispanic-American,
14 Asian American, and 53 from Crete. All patients met the
American College of Rheumatology criteria for the diagnosis of
SLE. Serum IFN-a activity is measured using a sensitive reporter cell
line (WISH cells) via assessment of IFN-a-induced gene transcription
in cells after exposure to serum. Mann-Whitney U was used for statistical comparisons between groups.
Results: Mean serum IFN-a activity levels were highest in subjects of
non-European ancestry (Asian-Americans - mean 26.76, AfricanAmericans mean 23.11, Hispanic-Americans mean 28.71).
European-Americans (mean 10.0) had statistically significantly lower
IFN-a activity than all of the non-European ancestry American groups
(p-values for all of these comparisons <0.001). Interestingly, the subjects from Crete had the lowest IFN levels (mean 1.3), and this was
statistically significantly lower than European-Americans (p0.005).
There was a non-significant trend toward a lower rate of antidsDNA antibody positivity in the subjects from Crete as compared
to European-Americans (p0.14).
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
10.1177/0961203314527038
9th European Lupus Meeting
450
Conclusion: European ancestry was associated with lower serum IFN-a
activity, and interestingly patients from Crete had lower IFN-a than
European-American patients. European-Americans represent a mix of
Northern and Southern European ancestry, and it is possible that
Southern European ancestry is associated with lower serum IFN-a.
It is also possible that environmental or disease activity factors play
a role in this finding.
A003
AUTOANTIBODIES TO THE CD94/NKG2A AND CD94/NKG2C
RECEPTORS IN PATIENTS WITH SLE
Hagberg N.1, Theorell J.2, Hjorton K.1, Eloranta M.-L.1,
Bryceson Y.T.2,3 and Ronnblom L.1
1
Uppsala University, Department of Medical Sciences, Uppsala, Sweden
2
Karolinska University Hospital, Department of Medicine, Huddinge,
Sweden 3University of Bergen, Institute for Clinical Sciences, Bergen,
Norway
Introduction: Recently, we identified a patient with systemic lupus erythematosus (SLE) that harbored autoantibodies to CD94/NKG2A.
CD94/NKG2A is an inhibitory NK cell receptor that binds HLA-E.
Aim: To investigate the occurrence and function of autoantibodies
targeting the CD94/NKG2A, CD94/NKG2C or NKG2D receptors
in patients with SLE.
Method: Sera from 203 SLE patients and 90 healthy individuals were
analyzed for Ig-binding to murine Ba/F3 cells transfected with CD94/
NKG2A, CD94/NKG2C or NKG2D, using flow cytometry. Identified
autoantibodies were characterized for interference with HLA-E-binding, effect on degranulation in response to HLA-E-transfected K562
cells, and their capacity to induce antibody-dependent cellular cytotoxicity (ADCC). The exons encoding NKG2A (KLRC1), NKG2C
(KLRC2), and CD94 (KLRD1) were sequenced. The titers of antiCD94/NKG2A and anti-CD94/NKG2C autoantibodies in longitudinally sampled sera were correlated to disease activity (SLEDAI) and
severity (SLICC/ACR damage index).
Results: Autoantibodies to CD94/NKG2A were found in sera from
seven patients. Six of these inhibited HLA-E-binding to CD94/
NKG2A, whereas one increased this binding. Two of these patients
sera also contained Ig that bound CD94/NKG2C, with one inhibiting,
and one augmenting, HLA-E-binding to CD94/NKG2C. Anti-CD94/
NKG2A and anti-CD94/NKG2C autoantibodies abrogated the HLAE-mediated inhibition of CD94/NKG2A and activation of CD94/
NKG2C NK cells, respectively. Furthermore, these autoantibodies
facilitated the elimination of CD94/NKG2A- and CD94/NKG2Cexpressing target cells through ADCC. No unique non-synonymous
sequence variations were found in KLRC1, KLRC2, or KLRCD1.
The titers of anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies were associated to disease activity.
Conclusions: Autoantibodies targeting the CD94/NKG2A or the
CD94/NKG2C receptor are found in a subset of SLE patients. Their
titers are associated to the disease activity and a more severe SLE
phenotype. Mechanistically, the autoabs can affect NK cell cytotoxicity and mediate ADCC. Consequently, anti-CD94/NKG2A and antiCD94/NKG2C autoabs may contribute to the pathogenesis of SLE
and our findings highlight the possible importance of NK cells in the
SLE disease process.
A004
AUTOPHAGY-MEDIATED TISSUE FACTOR RELEASE IN
LUPUS NEUTROPHIL EXTRACELLULAR TRAPS MAY
ACTIVATE THE COAGULATION CASCADE AND
CONTRIBUTE TO MICROVASCULAR INJURY
Frangou E.A.1, Kambas K.2, Gergianaki I.3, Karagiorgas F.1,
Karabela S.1, Bertsias G.3 and Boumpas D.T.1,3,4
1
Biomedical Research Foundation of the Academy of Athens, Athens,
Greece 2Democritus University of Thrace, Alexandroupolis, Greece
3
Institute of Molecular Biology and Biotechnology, Foundation of
Research and Technology-Hellas, Heraklion, Greece 4Medical School,
University of Athens, Athens, Greece
Introduction: Using microarrays, we have shown that active lupus
patients are characterized by a neutrophil signature and differential
expression of microRNAs and genes regulating autophagy. We have
also shown that tissue factor (TF), the main in vivo coagulation initiator, released on Neutrophil Extracellular Traps (NETs) activates the
coagulation cascade by generating thrombin, and activates platelets
and endothelial cells via PAR-1 signaling. We reasoned that in
lupus, autophagy mediates TF release in NETs leading to endothelial
injury.
Aim: To investigate the role of TF-decorated NETs in SLE.
Patients and Methods: Serum and neutrophils were isolated from 12
healthy donors and 10 active lupus patients. NETs were analyzed by
immunofluorescence for the co-localization of DNA with myeloperoxidase or TF. Healthy neutrophils were stimulated with lupus serum
with or without autophagy inhibitors. Autophagy was assessed by
immunoblotting for the conversion of LC3-I to LC3-II, and by LC3
immunofluorescence.
Results: Lupus neutrophils undergo increased spontaneous NET
release compared to healthy neutrophils. Moreover, healthy neutrophils treated with lupus serum exhibit increased autophagy and express
increased TF levels when compared to the effects of healthy serum. The
increase in TF by lupus serum is blocked by autophagy inhibitors.
Furthermore, healthy neutrophils treated with lupus serum exhibit
increased NET generation and TF-bearing NETs, both effects reversed
by autophagy inhibition. Ongoing experiments evaluate the presence of
TF-bearing NETs in the kidneys of lupus-prone mice and lupus nephritis patients, and the functional implications of TF-bearing NETs on
thrombin generation and activation of platelets and endothelial cells.
Conclusions: Lupus serum activates healthy neutrophils towards an
autophagy-mediated TF release in NETs which may activate the
coagulation cascade and contribute to microvascular injury.
Reference
1 Kambas K et al. Plos One 2012.
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A005
ELIMINATION OF GRANULOCYTIC-LIKE MYELOIDDERIVED SUPPRESSOR CELLS DUE TO EXTRACELLULAR
TRAP FORMATION IN LUPUS INFLAMMATORY MILIEU
Vlachou K.1, Fanouriakis A.2, Glymenaki M.1, Ioannou M.1,
Mintzas K.1, Boumpas D.T.1,3 and Verginis P.1,3
1
Laboratory of Autoimmunity and Inflammation, Institute of Molecular
Biology and Biotechnology, Heraklion 2Department of Rheumatology,
University of Crete Medical School, Heraklion, Greece 3Laboratory of
Cellular Immunology and Tolerance, Biomedical Research Foundation
Academy of Athens, Athens Greece
Introduction/Aim: Myeloid-derived suppressor cells (MDSCs) consist
of a heterogeneous population of myeloid cells that reside in the bone
marrow (BM) and give rise to macrophages, dendritic cells and granulocytes. They are characterized as CD11bhighGr-1 and are divided
into granulocytic-like (Ly6G) and monocytic-like (Ly6C) subsets
(G-MDSCs and M-MDSCs). MDSCs regulate both innate and adaptive responses. We have recently shown that G-MDSCs contribute to
the resolution of autoimmune inflammation within the central nervous
system. Herein, we sought to explore their role in systemic
autoimmunity.
Methods: Frequency and numbers of MDSCs in bone marrow (BM)
and spleens of F1 lupus mice were analyzed by flow cytometry. MDSC
function was determined by T cell proliferation using CFSE.
Extracellular Trap formation (ETosis) was assessed in G-MDSCs by
immunofluoresence staining with DAPI and myeloperoxidase (MPO)
or histone H3. Frequency of HLA-DRintCD14-CD33CD15 MDSCs
in peripheral blood of SLE patients was determined by flow cytometry.
Results: Compared to mice with encephalomyelitis, we found decreased
frequency of MDSCs in the BM and spleens of F1 lupus mice with
established proteinuria. The frequency of MDSCs was not significantly
elevated in active SLE patients as compared to inactive patients. Sorted
MDSCs from lupus mice showed an impaired ability to suppress T cell
responses in vitro. Interestingly, G-MDSCs from F1 lupus mice exhibited increased spontaneous ETosis in contrast to G-MDSCs from naive
C57BL/6 mice. Treatment of naive B6-derived G-MDSCs with serum
from diseased F1 mice but not from healthy controls significantly
induced increased ETosis.
Conclusion: The lupus microenvironment promotes G-MDSCs spontaneous ETosis resulting in decreased frequency and numbers.
Delineation of the molecular mechanism that promotes NETosis in
G-MDSCs in the context of SLE would provide meaningful insights
in the regulation of aberrant autoimmune responses.
A006
ENDOTHELIN 1 IN SYSTEMIC LUPUS ERHYTEMATOSUS
NOT JUST A LOCAL PATHOGEN?
Saulescu I.1, Banica L.2, Matache C.2, Opris D.1, Groseanu L.1,
Borangiu A.1 and Ionescu R.1
1
UMF Carol Davila Sf. Maria Hospital, 2Cantacuzino Institute
Background: Endothelin 1 (ET-1) is an important factor for vascular
dysfunction, in rheumatology being mostly investigated in systemic
sclerosis. In vitro data showed that alpha Interferon (IFN) can
induce production of ET-1, alpha IFN being recognized as one of
the corn-stone molecule in SLE. This suggests interplay between
them in SLE systemic endothelial dysfunction.
Objective: to evaluate mRNA ET-1 expression in a SLE cohort ands its
correlation with IFN inducible genes and SLE characteristics.
Material and methods: we evaluated 20 patients with SLE and 12
matched by gender and age healthy donors. All subjects gave informed
consent for all procedures. A complete evaluation of SLE patients was
made. mRNA levels for Endothelin-1 and IFN inducible genes IFIT1
and Mx1 in peripheral blood mononuclear cells (PBMC) were evaluated. The statistical analysis was made with SPSS programme.
Results: Levels of mRNA for ET-1 and alpha IFN inducible genes were
significant higher in SLE then in healthy subjects (p<0.05). Moreover,
we found significant correlation between expression for ET-1 and Mx1 in SLE group (p0.037). ET -1 expression was correlated with renal
involvement (p0.021). The systemic effect of ET-1 is suggested also by
the correlation between ET-1 expression and fatigue (p 0.007), this
might being a reflection of high serum level of ET-1 and its effect on
muscle oxygen supply.
Conclusions: High mRNA ET-1 expression in SLE patients was correlated with Mx-1 as part of the IFN inducible genes and also with renal
involvement and fatigue. This study shows that ET-1 could represent
an important pathway for systemic endothelial damage that appears
in SLE.
Bibliography
1 George P.M., Cunningham M.E., et al. Endothelin-1 as a mediator
and potential biomarker for interferon induced pulmonary
toxicityPulmonary Circulation 2012; 4: 501504.
2 Alvarez D, Briassouli P, et al. A novel role of Endothelin-1 in
linking Toll Like Receptor7 mediated inflammation to fibrosis in
congenital heart blockJ.Biol. Chem 2011; 286: 3044430454.
A007
FOXP3 TREGS MODULATE DC AUTOPHAGY IN A

CONTACT-DEPENDENT FASHION
Alissafi T.1,2, Ioannou M.1, Hatzioannou A.2, Boon L.3, Grun R. J.4,
Grutzkau A.4, Chavakis T.5 and Verginis P.1,2
1
Institute of Molecular Biology and Biotechnology, Foundation for
Research and Technology, 71300 Heraklion, Greece 2Biomedical
Research Foundation, Academy of Athens, 11527 Athens, Greece
3
Bioceros BV, 3584 CM Utrecht, Netherlands 4Institute of Infection
Immunology, TWINCORE, 30625 Hannover, Germany 5Department of
Clinical Pathobiochemistry, Institute for Clinical Chemistry and
Laboratory Medicine and Department of Internal Medicine, University
Dresden, 01307, Dresden, Germany
Introduction: Foxp3 regulatory T cells (Tregs) are crucial for the
establishment of tolerance and thus, hold promise for the design of
immune-based therapies. However this effort has been hampered by
major caveats including the lack of understanding of their molecular
and cellular targets in an un-manipulated wild-type (WT) immune
repertoire.
Aim: To identify novel molecular and cellular targets of Treg-mediated
suppression in an intact immune system.
Methods: Induction of Foxp3 Treg-mediated tolerance in WT mice
was performed utilizing a novel method for sub-immunogenic delivery
of antigen with the use of implanted micro-osmotic pumps. Flow cytometry was used for determining the individual cellular subsets and cell
sorting and MACS beads for their isolation. Determination of autophagic markers was performed using western blotting and immunofluorescent stainings visualized with confocal.
Results: Our results pointed dendritic cell (DC) autophagy as a novel
molecular target of Foxp3 Tregs. De novo generated Foxp3 Tregs
targeted the antigen-bearing inflammatory CD11cCD11bGr1 DCs
(iDCs) by diminishing their accumulation in the draining lymph nodes
(dLNs) and by decreasing the induction of their autophagic pathway.
Furthermore, ex vivo isolated Foxp3 Treg-exposed DCs demonstrated impaired recruitment of the autophagosome protein LC3 to
antigen-containing phagosomes. Finally, we revealed that Foxp3
Treg-mediated regulation of autophagy in CD11c DCs in vivo was
IL-10 independent but LFA-1 and CTLA-4-dependent.
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452
Conclusions: Collectively, our data decipher DC autophagy as a novel
Foxp3 Treg-mediated molecular target of immune suppression that
could be exploited for potential therapeutic interventions.
A008
HUMAN CATHELICIDIN IN SLE: ONE LINK BETWEEN
INNATE IMMUNE SYSTEM AND VASCULAR DYSFUNCTION
Saulescu I.1, Banica L.2, Matache C.2, Stavaru C.2, Opris D.1,
Groseanu L.1, Borangiu A.1 and Ionescu R.1
1
UMF Carol Davila Sf. Maria Hospital, 2Cantacuzino Institute
Background: Type I interferons (IFNs) are one of the innate immunity
mediators that are important players in SLE pathogenesis, contributing
both to autoantibody response and vascular dysfunctions. Nowadays a
special attention is given to the human cathelicidin (hCAP/LL-37) as
major inducer of type I IFN. LL-37 acts like an imunomodulator, displaying cytotoxic and chemotactic activities and modulating apoptosis.
Objective: To evaluate mRNA expression of hCAP18 in a SLE peripheral blood mononuclear cells (PBMCs) in correlation with IFN signature genes, autoantibody response and vascular damage.
Material and methods: Twenty SLE patients and 12 healthy donors
(HD) were enrolled. A complete evaluation of SLE patients was
made. The expression of mRNA for hCap18 and for IFN signature
genes (IFIT1 and Mx1) in PBMCs was evaluated by realtime PCR.
The statistical analysis was performed with SPSS.
Results: Expression of mRNA for hCAP18 was higher in SLE population
than in HD (p0,055) and strongly correlated with IFN inducible gene
Mx1 (p0.004) and with low levels of HDL cholesterol (p0.031). A
direct correlation was identified between hCAP18 and anti-Ro antibodies
(p 0.024). We establish an arbitrary score for antinuclear antibodies: antidsDNA, anti-Sm and anti-Ro antibody and a direct correlation of that
and hCAP18 mRNA level was identified (p0.048). In contrast, hCAP18
level was inversely correlated with SLICC damage index score calculated
only for vascular damage (p0.038).
Conclusion: hCap18 is highly expressed in SLE patients being involved
in the antibody production. Up-regulation of hCAP18 mRNA in SLE
PBMCs seems to be induced together with that of IFN signature genes.
In contrast hCAP18 expression was inversely correlated with vascular
damage. This effect might be the effect of direct action on endothelial
cells (ECs), reducing their apoptosis and inducing the differentiation of
mature ECs from ECs progenitors.
Bibliography
1 Mocsai A. Diverse novel functions of neutrophils in immunity,
inflammation and beyond. J. Exp. Med 2013; 7: 12831299.
A009
IFNa INDUCED DIFFERENTIATION AND MATURATION OF
SLE MONOCYTES ARE SUBJECTED TO AUTOPHAGIC
CONTROL
Gkirtzimanaki K.1, Kabrani E.1, Gergianaki I.2, Bertsias G.1,
Boumpas D.1,3 and Verginis P.1,3
1
Laboratory of Autoimmunity & Inflammation, IMBB, Heraklion,
Greece 2Department of Rheumatology, UoC Medical School, Heraklion,
Greece 3Laboratories of Inflammation and Autoimmunity, and Cellular
Immunology &Tolerance, BRFAA, Athens, Greece
Introduction: IFNa, a key pathogenic cytokine in SLE, is a potent
inducer of monocyte differentiation into highly activated and partially
mature dendritic cells that secrete large amounts of pro-inflammatory
cytokines and sustain IFNa expression in an autocrine fashion. Recent
data implicate autophagy in the survival and differentiation of monocytes and presentation of self-antigens. Thus, we reasoned that autophagy may mediate the effects of IFNa on SLE monocytes.
Aim: To dissect the molecular mechanism governing IFNa-induced

differentiation of SLE monocytes and investigate its role in self-antigen
presentation.
Methods: Peripheral blood CD14 monocytes and sera from 15 active
SLE patients (females, ANA with lupus nephritis) and 10 age matched
healthy controls were studied. Healthy monocytes were incubated with
rIFNa or SLE serum and autophagy induction was assessed by immunoblotting and immunofluorescence. Ex vivo induced monocyte differentiation, maturation and mitochondrial function were analysed by flow
cytometry and immunofluorescence. Chloroquine and wortmanin were
used as autophagy inhibitors and B18R as IFNa soluble receptor.
Results: In IFNa-treated healthy primary monocytes, kinetics of LC3I,
LC3II and p62 levels and LC3 localization indicate induced activation of
the autophagic machinery. Upon treatment with rIFNa or lupus serum,
monocytes lose CD14 expression and upregulate HLA-DR, CD86, and
CD83 levels in an autophagy dependent way, since inhibition of autophagy abolishes their differentiation and partial maturation. Interestingly,
autophagy upregulation in rIFNa or SLE serum treated monocytes lead
to comparable changes in mitochondrial functionality to those observed
in SLE monocytes, including changes in ROS production, mitochondrial
polarization and VDAC protein levels. Work in progress, addresses the
contribution of the IFNa-autophagy axis in lupus autoreactivity by
assessing its impact on the cytosolic release of endogenous, oxidized
mitDNA and autologous T-lymphocyte reactions.
Conclusion: IFNa induces monocyte differentiation and maturation in
an autophagy-mediated manner, affects mitochondrial quality control,
and may promote lupus autoreactivity.
A010
IMPAIRED DEGRADATION AND ABERRANT
PHAGOCYTOSIS OF NECROTIC CELL DEBRIS IN THE
PERIPHERAL BLOOD OF PATIENTS WITH SLE
Vakrakou A.G.1 and Manoussakis M.N.1,2
1
Department of Pathophysiology, School of Medicine, University of
Athens, Greece 2Hellenic Pasteur Institute, Athens, Greece
Introduction and Aim: Aberrant removal of necrotic debris is considered a feature with inflammatory consequences in SLE. Herein,
SLE patients were investigated for the capacity of their sera to degrade
secondary necrotic cell remnants (SNEC) and DNA (endonuclease
DNase1 activity), as well as for uptake of SNEC by blood-borne
phagocytes (SNEC-phagocytosis).
Patients: For comparison, specimens from unselected RA patients and
from healthy blood donors (HBD) were also studied.
Results: Compared to HBD, the sera from SLE patients (but not RA)
were found to exhibit significantly impaired capacity for degradation
of SNEC (p0.008) and deficient DNase1 activity (p<0.0001) that
correlated inversely with the SLEDAI activity index (r -0,457,
p0.03). Ex-vivo whole blood analyses indicated that SLE patients
(but not RA) also manifested significantly increased SNEC-phagocytosis by monocytes and granulocytes (p<0.0001) that correlated with
SLICC disease severity index (p0.01). Such aberration was largely
found to reside in patients sera and particularly the IgG. In crossadmixture experiments, the sera of SLE patients (but not of RA)
induced significant SNEC-phagocytosis by normal monocytes that
correlated inversely with the DNase1 activity (p<0.0001) and the capacity for SNEC degradation (p<0.05) of these sera. In line with this,
the inhibition of DNase1 in HBD sera by G-actin was found to lead to
significantly diminished SNEC degradation and increased SNEC
uptake by healthy phagocytes (p0.0009), supporting the important
physiologic role of serum DNase1 in the prevention of SNEC-phagocytosis. Purified serum IgG from SLE patients manifested increased
binding to SNEC and, upon addition to HBD serum, prevented the
physiologic SNEC degradation and increased SNEC uptake by healthy
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453
phagocytes, most likely due to shielding of SNEC against endonuclease digestion.
Conclusions: These data indicate that upon cell necrosis, the immune
system of SLE patients may be overly exposed to the necrotic debris
and thus initiate a profound inflammatory response to tissue injury.
A011
INCREASED EXPRESSION OF LOW DENSITY

GRANULOCYTES IN JUVENILE ONSET SYSTEMIC LUPUS
ERYTHEMATOSUS (JSLE) PATIENTS CORRELATES WITH
DISEASE ACTIVITY
Midgley A.1 and Beresford M.W.1,2
1
Department of Womens and Childrens health, University of Liverpool,
UK 2Department of Paediatric Rheumatology, Alder Hey Childrens
NHS Foundation Trust, Liverpool, UK
Introduction: Neutrophils are critical components of the innate immune
system, however they are implicated in a wide range of non-infectious
inflammatory conditions [1]. The second most prevalent transcriptional signature in JSLE patients corresponds to neutrophil-specific
genes where differential expression of these genes correlate with disease
activity [2]. A subset of neutrophils in the peripheral circulation of SLE
patients has been described [2] and termed low density granulocytes
(LDG).
Aim: To measure the expression of LDG in JSLE patients compared to
controls and any correlations with disease activity.
Patients and Method: Neutrophils and LDGs were isolated from JSLE
(n8) and paediatric non inflammatory control patients (n10) by
one-step centrifugation through polymorph prep or histopaque gradient respectively. Cell populations were assessed and compared using
flow cytometry and morphological analysis of cytospin preparations.
Standard clinical data which included disease activity markers/scores
were collected for each patient. Spearmans rank correlation coefficient
was used to assess any correlations between disease activity markers
and LDG expression.
Results: Significantly increased LDG expression (%meanSEM,
range) was observed in JSLE patients (11.683.4, 3.41-30.3) compared
to controls (2.410.54, 0.36-5.27; p<0.05). A statistically significant
positive correlation was observed between LDG expression and disease
activity indices BILAG (correlation coefficient 0.97; p<0.001) and
SLEDAI (correlation coefficient 0.79; p<0.05) and the biomarker of
dsDNA-antibodies (correlation coefficient 0.870; p<0.05).
Conclusion: Here we observe increased expression in an abnormal
subset of neutrophils in JSLE patients, which correlate with dsDNA
antibody concentration and scores of disease activity. These correlations indicate that the increased LDG expression observed in this
study may have a potential role in the pathogenesis of JSLE.
Investigating the morphology and characteristics of these cells will
determine whether LDG represent a distinct population of lupus neutrophils with specific disruptions in neutrophil development or a more
activated subset present in JSLE patients.
References
1 Dallegri
F., Ottonello
L. Tissue injury in neutrophilic
inflammationInflamm Res 1997; 46(1038291): p. .
2 Bennett L., et alInterferon and granulopoiesis signatures in systemic
lupus erythematosus bloodJ Exp Med 2003; 197(671123): p. .
A012
JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS SERUM
REDUCES PHAGOCYTIC ACTIVITY OF HEALTHY
POLYMORPHONUCLEAR CELLS
Sampath S.1,2, Midgley A.1, Ballantine L.1 and Beresford M.1,2
1
University of Liverpool, Department of Womens and Childrens
Health, Institute of Translational Medicine, Liverpool, UK 2Alder Hey
Childrens NHS Foundation Trust, Department of Paediatric
Rheumatology, Liverpool, UK
Introduction: Children with lupus have more severe disease onset and
greater mortality than adults (1,2,3). Phagocytic function of polymorphonuclear cells (PMNs) is defective in adult-onset systemic
lupus erythematosus (SLE), resulting from both cell mediated and
humoral factors (4,5). There is limited data regarding neutrophil phagocytosis within juvenile-onset SLE (JSLE).
Aim: This study aimed to analyse the effect of JSLE serum on phagocytic function of PMNs derived from healthy controls.
Methods: PMNs were isolated from blood of healthy control subjects.
Phagocytosis was measured using pHrodo labelled E.Coli incubated
with isolated PMNs either on ice (negative control) or at 37 C for 30
minutes with 10% control and JSLE serum. pHrodo, a pH-sensitive
fluorescent dye emits fluorescence at low pH levels occurring postphagocytic fusion of phagosome with the lysosome, quantified by
flow-cytometer. Percentage of PMNs phagocytosing labelled E.Coli
were determined and expressed as mean SD.
Results: JSLE serum from 6 patients and total of 10 different clinical
episodes were investigated. Mean (SD) phagocytosis was
42.7(16.5)% and 53.7(16.4)% with JSLE and control serum
respectively. PMNs incubated with JSLE serum had 11% (
12.46%) less phagocytosis compared to control serum, see Table 1.
Disease activity of each of the 10 clinical episodes was measured
using British Isles Lupus Assessment (BILAG) index. There was moderate negative correlation (spearmans rank correlation coefficient, r0.45, p0.18) between the disease activity scores and the phagocytic
activity; 28% of variation in phagocytosis could be explained by
BILAG scores, coefficient of determination, r20.28.
Conclusion: JSLE serum reduces the phagocytic ability of healthy neutrophils, whilst patient disease activity had a trend towards moderate
negative correlation with this reduction in phagocytosis. As previous
work has demonstrated significantly increased levels of apoptotic cells
in JSLE patients, future investigation will analyse whether JSLE serum
has an effect on the ability of neutrophils to phagocytose apoptotic
cells.
Table 1.
JSLE clinical episodes
% Change in phagocytosis
with JSLE serum compared
to corresponding control serum
BILAG numerical
2004 score
1
2
3
4
5
6
7
8
9
10
24
8.9
30.8
10.4
8.9
25.7
3
0.8
9.1
8.6
13
0
3
3
9
10
1
5
1
3
Mean change in phagocytosis was -11%, SD 12.46%

Moderate negative correlation between reduction in phagocytosis and
disease activity score (BILAG), Spearmans rank correlation coefficient,
r -0.45, p0.18.
Lupus
454
References
1 Tucker LB, Uribe AG, Fernandez M, et al. Adolescent onset of
lupus results in more aggressive disease and worse outcomes:
Results of a nested matched case-control study within LUMINA,
a multiethnic US cohort (LUMINA LVII). Lupus 2008; 17:
314322.
2 Linda T H, et al. Clinical and Laboratory Characteristics and LongTerm Outcome of Pediatric Systemic Lupus Erythematosus: A
Longitudinal Study. The Journal of Pediatrics.April 2008.
3 Aimee O H, et al. CHildhood-onset Disease Predicts Mortality in
an Adult Cohort of patients with systemic lupus erythematosus.
Arhritis Care Res (Hoboken) 2010 August; 62(811521159.
4 Brandt L, Hedberg H.. Impaired phagocytosis by peripheral blood
granulocytes in systemic lupus erythematosus. Scandinavian journal
of haematology 1969; 6(534853. (Epub 1969/01/01.
5 Janko C, Schorn C, Grossmayer GE, Munoz LE. Inflammatory
clearance of apoptotic remnants in systemic lupus erythematosus
(SLE). Autoimmun Rev 2008; 8: 912. 22.
A013
PATHOGENIC ROLE OF IL-10 PRODUCING HELPER T CELLS
IN SYSTEMIC LUPUS ERYTHEMATOSUS
Penatti A.E.1, Facciotti F.2, Zeni S.3, Abrignani S.2, Meroni P.L.1 and
Geginat J.2
1
Dept. Clin. Sciences & Comm. Health, University of Milan, G. Pini
Institute, Rheumatology Dept., Milan, Italy 2INGM, National Institute
of Molecular Genetic, Autoimmunity Unit, Milan, Italy, 3 G. Pini
Institute, Rheumatology Dept., Milan, Italy
Introduction: IL-10 is a potent anti-inflammatory cytokine that contributes to the suppressive functions of regulatory T-cells, but it is also
a well-known B cell growth and differentiation factor produced by
CD4 helper T-cells. Consequently, IL-10 is pathogenic in systemic
lupus erythematosus (SLE) where it promotes autoantibody production and nephritis. We have previously shown that human CCR6
memory T cells produce IL-10 in secondary lymphoid organs, and
more recently we found that they promote B cell antibody production
via IL-10, but are distinct from follicular helper (TFH) and Th17 cells.
Aim: To monitor the frequency and function of IL-10-producing B
helper T cells in SLE patients and to evaluate their association with
disease activity.
Patients and Methods: Blood samples from 40 clinically well-characterized SLE patients and 25 healthy donors (HD) were included.
Composition of different T cell subsets in peripheral blood according
to surface markers expression and intracellular cytokine production
were assessed by flow cytometry. The frequencies of T cell subsets
were correlated with disease activity (measured by the SELENASLEDAI index). To assess B helper functions, T cell subsets and B
cells from SLE patients and HD were co-cultured ex vivo and IgG
production was measured in supernatants by ELISA.
Results: IL10-producing CCR6 memory T cells, but not TFH cells
were significantly expanded in the peripheral blood of SLE patients as
compared to HD. Importantly, the frequency of CCR6 memory T
cells and serum levels of IL-10, but not of IL-17, correlated with disease activity. Ex vivo sorted CCR6 helper T cells from blood of SLE
patients produced high levels of IL-10 upon co-culture with B cells and
promoted IgG production. Strikingly, CD25 Tregs suppressed B cell
help provided by CCR6 T cells in HD, but not in SLE patients.
Conclusion: Our results demonstrated that accumulation of IL-10-producing CCR6CD4 memory T cells correlates with SLE disease
activity, supporting a pathogenic role of these helper T cells. This
hypothesis is corroborated by functional experiments, which demonstrate a Treg-resistant B helper capacity of IL-10-producing CCR6 T
cells in SLE patients. Therefore, CCR6IL10-producing helper T cells
represent a potential therapeutic target and/or diagnostic/prognostic
marker of disease activity in SLE patients.
A014
THE EFFECTS OF VITAMIN D SUPPLEMENTATION ON
T-CELLS IN PATIENTS WITH SYSTEMIC LUPUS
ERYTHEMATOSUS
Piantoni S.1,2, Zanola A.1, Andreoli L.1, DallAra F.1,2, Scarsi M.1 and
Tincani A.1
1
Rheumatology and Clinical Immunology, Spedali Civili and University
of Brescia, Italy, 2University of Pavia, Italy
Introduction: In addition to the classic role of vitamin D(VD)on bone
metabolism, many data have underlined its pleiotropic effects on different cellular types, including those of the immune system. Recent
studies demonstrate that VD may have an action on T cells, inhibiting
Th-1 and Th-17 response and enhancing Th-2 and T-regulatory function. After repeated antigenic presentation, T-cells undergo a downmodulation of CD28, leading to the peripheral expansion of a subpopulation with cytotoxic activity:the CD28-T cells. At the best of our
knowledge, little is known about the effect of VD on CD28- and
memory T-cells.
Aim: To study the effect of VD supplementation on the circulating
levels of different T-cells subsets, and on cytokines production in 34
patients with Systemic Lupus Erythematosus(SLE).
Patients and Methods: 16 patients were supplemented for 12 months
with an intensive regimen(IR) of cholecalciferol(300.000UI for the first
month and 50.000UI/monthly), and 18 patients with a standard
regimen(SR)(25.000UI monthly). Phenotypic analysis of peripheralT-lymphocyte and the intracytoplasmatic production of IL-4 and gIFN from peripheral blood mononuclear cells was evaluated by flowcytometry.
Results: After 12 months of treatment, a significant increase in the
number of peripheral induced Treg cells(CD25highCD127lowCCR7-)
was observed in both groups of treatment. Furthermore an increase in
the total amount of circulating CD4CD45RACCR7- effectormemory-T-cells was seen. A reduction of the CD8CD28-T-cells in
SLE patients was demonstrated only in the SR group (Table 1). In the
IR group of patients evaluated for cytokines production(n8), a reduction of g-IFN/IL-4(from 12.1 to 3.2; p0.01) among CD8T-cells was
detected.
Conclusion: VD may promote the enhancement of peripheral induced
Treg cells and the production of Th2 cytokines.
Table 1.
IR
Cell phenotype
T0
SR
T12 p
T0
T12 p
TREG CCR7-(% TREG)

30.9 34.8 0,01
25.3 34.7 0,03
T CD4CD45RACCR7-(cell/ml) 6
9.2 <0.01 7.7 16.9 <0.01
TCD8CD28-(% CD8)
24.9 24.7
ns
26.7 19 0,01
References
1 Strioga M. Immunology 2011; 134 (1): 17-32; Terrier B et al.
Arthritis Res Ther 2012; 14: R221.
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A015
A016
THE IMPLICATION OF NETS ON THE UPREGULATION OF

MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN LUPUS
NEPHRITIS
Vernon A.1, Midgley A.1 and Beresford M.W.1,2
1
Institute of Translational Medicine (Child Health), University of
Liverpool, UK 2Department of Paediatric Rheumatology, Alder Hey
Childrens Hospital, Liverpool, UK
THE INTERLEUKIN-6/INTRELEUKIN-6-RECEPTOR SYSTEM

IS UPREGULATED IN SLE, BUT SHIFTED TOWARDS TRANSSIGNALLING
Skwarek M., Fantana J., Heschel B. and Aringer M.
Division of Rheumatology, Department of Medicine III, University
Clinical Center Carl Gustav Carus at the Technical University of
Dresden, Germany
Introduction: Monocyte chemoattractant protein-1 (MCP-1) has been

identified as a biomarker of lupus nephritis (LN), up-regulated in the
active disease.[1] It is involved in the early recruitment of pro-inflammatory cells to the kidney[2], resulting in further renal damage.
Neutrophils can undergo a process called NETosis, which results in
the release of neutrophil extracellular traps (NETs)[4]. Impairment of
NET degradation is associated with LN.[5]
Aim: To use an in vitro model of LN to assess the effect of NETs on
the production of MCP-1 by podocytes.
Methods: Human podocyte cell-line with human-monocyte derived
macrophages was used to create an in vitro model of (LN). Human
monocytes were differentiated into macrophages using media containing monocyte colony stimulating factor. NETs were induced from
isolated neutrophils using 600nm PMA. The macrophages were then
either unstimulated (inactive cells) or incubated with IFN-g at a concentration of 1ng/ml (active cells)/- NETs. After 48 hours the supernatant from the macrophages /- NETs was removed and added to
mature podocytes. MCP-1 concentration (meanSEM) was measured
using ELISA. Podocytes following culture were visualised using light
microscopy.
Results: There was no difference in the concentration of MCP-1 from
podocytes alone (1968101pg/mL) compared to in the presence of
inactive macrophages (1860135pg/mL; p0.373). However, there
was significantly increased MCP-1 from the podocytes was produced
following the addition of active macrophages (3874292pg/mL;
p0.035) or NETs (4279181pg/mL: p0.011). When cultured
together with active macrophages and NETs, the podocytes produced
the highest concentration of MCP-1 (4716420pg/mL; p0.033).
Conclusion: Using an in-vitro model of LN, co-culture of human podocyte cells and active macrophages resulted in significant up-regulation
of MCP-1 production. The addition of NETs further increases this upregulation and dramatically changes the morphology of the podocytes.
Introduction: Interleukin-6 (IL-6) is closely linked to CRP, but this

seems not to hold true in SLE. IL-6 exerts its functions by binding
to a receptor consisting of CD130 and membrane-bound IL-6 receptor
(CD126), which is found on hepatocytes and leukocytes, or soluble IL6 receptor (sIL-6R).
Aim: To investigate the IL-6/IL-6R system in SLE.
Patients and Methods: Lymphocytes of 50 SLE patients were compared
to those of 68 healthy individuals (HC). Peripheral blood mononuclear
cells (PBMC) were immediately prepared from peripheral venous
blood and stained with PE-labelled anti-CD126 or anti-CD130 or control antibodies. Serum levels of IL-6 and soluble IL-6 receptor (sIL-6R)
were measured by ELISA. The values where correlated with each other
and disease activity score (ECLAM).
Results: Serum IL-6 levels of SLE patients were higher than those of
HC (3 (0.5-69.3)(median (range)) vs. 0 (0-4.8) pg/ml, p<0.0001).
Lower percentages of lymphocytes of SLE patients than of HC
expressed CD126 (4917 (meanSD) vs. 608%, p<0.0001) and
CD130 (4919% vs. 5910%, p0.003). CD126 and CD130 were
closely correlated (Pearson r0.79, p<0.0001).In contrast to the membrane-bound receptors, serum sIL-6R was increased in SLE as compared to HC (45.1 (20.8-109.6)(median (range)) vs. 38.1 (18.1-57) ng/
ml, p0.02). There was a trend towards a correlation between sIL-6R
and disease activity by ECLAM (Spearman r-0.3, p0.056).
Conclusions: In line with published data, IL-6 is upregulated in SLE.
The decrease of both membrane bound IL-6 receptor chains, together
with the increase in soluble IL-6 receptors suggests that trans-signalling
via sIL-6R may dominate in SLE, possibly shifting IL-6 effects from
hepatocytes (carrying CD126), and thus from CRP producti
References
1 Watson L., Midgley A., Pilkington C., Tullus K., Marks S. D.,
Holt R. C. L., Jones C. A., Beresford M. W. Urinary monocyte
chemoattractant protein 1 and alpha 1 acid glycoprotein as biomarkers of renal disease activity in juvenile-onset systemic lupus
erythematosus. Lupus 2012; 21: 496501.
2 Watson L., Beresford M. W.. Urine biomarkers in juvenile-onset
SLE nephritis. Pediatric Nephrology 2013; 28: 363374.
3 Belot, A. and Cimaz, R. (2012) Monogenic forms of systemic lupus
erythematosus: new insights into SLE pathogenesis. Pediatric
Rheumatology. 10.
4 Remijsen Q., Kuijpers T. W., Wirawan E., Lippens S.,
Vandenabeele P., Vanden Berghe T.. Dying for a cause:
NETosis, mechanisms behind an antimicrobial cell death modality.
Cell Death Differ 2011; 18: 581588.
5 Hakkim A., Furnrohr B. G., Amann K., Laube B., Abed U. A.,
Brinkmann V., Herrmann M., Voll R. E., Zychlinsky A..
Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proceedings of the National Academy
of Sciences of the United States of America 2010; 107: 98139818.
A017
TLR8 ON DENDRITIC CELLS AND TLR9 ON B CELLS
RESTRAIN TLR7-MEDIATED SPOTANEOUS
AUTOIMMUNITY IN C57BL/6 MICE
Desnues B.1, Macedo A.B.1, Roussel-Queval A.1, Bonnardel J.1,
Henri S.1, Demaria O.1,2 and Alexopoulou L.1
1
Centre dImmunologie de Marseille-Luminy, Aix-Marseille University
UM2, INSERM U1104, CNRS UMR 7280, 13288 Marseille, France;
2
University Hospital CHUV, Lausanne, Switzerland.
Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical presentations characterized by the
presence of autoantibodies to nuclear components. TLR7, TLR8 and
TLR9 sense microbial or endogenous nucleic acids and are implicated
in the development of SLE. In mice TLR7-deficiency ameliorates SLE,
while TLR8- or TLR9-deficiency exacerbates the disease due to increased
TLR7 response1. Thus, both TLR8 and TLR9 control TLR7 function.
Aim: To study whether TLR8 and TLR9 act in parallel or in series in
the same or different cell types in controlling TLR7-mediated lupus.
Methods: By analyzing TLR8-, TLR9- and double TLR8/9-deficient
mice and primary cells we evaluated SLE development and immune
responses.
Results: We found that double TLR8/9-deficient (TLR8/9-/-) mice on
the C57BL/6 background showed increased abnormalities characteristic of SLE, including splenomegaly, autoantibody production, frequencies of marginal zone and B1 B cells and renal disease compared to
Lupus
456
single TLR8-/- or TLR9-/- mice. On the cellular level, TLR8-/- and
TLR8/9-/- dendritic cells were hyperesponsive to TLR7 ligand R848,
while TLR9-/- cells responded normally. Moreover, B cells from
TLR9-/- and TLR8/9-/- mice were hyperesponsive to R848, while
TLR8-/- B cells not.
Conclusion: Our results reveal that TLR8 and TLR9 have an additive
effect on controlling TLR7 function and TLR7-mediated lupus, however, they act on different cell types2. TLR8 controls TLR7 function on
dendritic cells, while TLR9 restrains TLR7 response on B cells.
References
1 Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N,
Murphy AJ, Valenzuela DM, Yancopoulos GD, Flavell RA,
Alexopoulou L. TLR8 deficiency leads to autoimmunity in mice.
J Clin Invest 2010; 120: 365162.
2 Desnues B, Macedo AM, Roussel-Queval A, Bonnardel J, Henri
S, Demaria O, Alexopoulou L. TLR8 on dendritic cells and TLR9
on B cells restrain TLR7-mediated spontaneous autoimmunity in
C57BL/6 mice. Proc Natl Acad Sci U S A 2014; 111: 1497502.
A018 COPYRIGHT PROTECTED. NOT FOR PUBLICATION
Genetics and -omics (genomics, metagenomics,

proteomics, metabolomics)
A019
EFFECT OF SINGLE-NUCLEOTIDE POLYMORPHISMS ON
TYPE I INTERFERON PRODUCTION BY PLASMACYTOID
DENDRITIC CELLS STIMULATED WITH SLE-ASSOCIATED
IMMUNE COMPLEXES
Berggren O.1, Alexsson A.1, Tandre K.1, Syvanen AC.2, Ronnblom L.1
and Eloranta ML.1
1
Uppsala University, Dept. of Medical Sciences, Rheumatology and
Science for Life Laboratory, Uppsala, Sweden 2Uppsala University,
Dept. of Medical Sciences, Molecular Medicine and Science for Life
Laboratory, Uppsala, Sweden
Introduction: Systemic lupus erythematosus (SLE) and many other systemic autoimmune diseases have a persistently activated type I interferon (IFN) system, displayed as elevated serum levels of IFN-a and
increased expression of type I IFN inducible genes (an IFN signature).
Lately, studies have shown an association between the susceptibility to
SLE and several gene variants within the type I IFN system, and we
have showed that IFN-a production by the plasmacytoid dendritic
cell (pDC) was enhanced by crosstalk with natural killer (NK) cells
and B cells.
Aim: We investigated whether single nucleotide polymorphisms (SNPs)
associated with SLE and other autoimmune diseases have an impact on
the IFN-a production by pDC.
Methods: pDC, B and NK cells were isolated from peripheral blood
obtained from healthy individuals, and stimulated with RNA-containing immune complexes (IC), herpes simplex virus (HSV) or the oligonucleotide ODN2216. IFN-a production was measured in the cell
cultures by an immunoassay. All blood donors were genotyped with
200K ImmunoChip and a 5bp CGGGG length polymorphism in the
IFN regulatory factor 5 gene (IRF5) by PCR.
Results: We found associations between IFN-a production and
28-107 SNPs (p<0.001) depending on the combination of stimulated
cell types. However, only three of these associated SNPs were
shared between the cell type combinations. Several of the SNPs have
not been associated with type I IFN production previously, while
some loci have been described earlier for their genetic association
with SLE. Furthermore, we found that the SLE-risk variant of the 5
bp IRF5 CGGGG-indel was associated with a lower IFN-a

production.
Conclusion: We found a large number of genetic variants affecting the ICmediated type I IFN production that highlight the intricate regulation of
the type I IFN system and can reveal new therapeutic targets for SLE.
A020
GENE POLYMORPHISM OF CYTOKINES IL-17, IL-23 AND
TGF-b IN SERBIAN PATIENTS WITH ATIPHOSPHOLIPID
SYNDROME
Popovic-Kuzmanovic D.1, Stojanovich L.1, Novakovic I.2,
Aksentijevich I.3, Zogovic N.4, Tovilovic G.4 and Trajkovic V.5
1
Bezhanijska Kosa University Medical Center, Belgrade, Serbia
2
Institute of Biology, School of Medicine, University of Belgrade,
Belgrade, Serbia 3Genetics and Genomics Branch, National Institute of
Arthritis, Musculoskeletal, and Skin Diseases, NIH, Bethesda, MD,
USA 4Institute of Biological Research, University of Belgrade, Belgrade,
Serbia 5Institute of Microbiology and Immunology, School of Medicine,
Belgrade, Serbia
Aim: To investigate the serum concentrations of cytokines IL-17, IL-23
and TGF-b and gene polymorphisms as susceptibility markers for
Primary Antiphospholipid Syndrome (PAPS) in Serbian population.
Controlling the expression and production of these cytokine may be a
new approach to the treatment of PAPS and gene polymorphisms can
influence the risk of illness.
Material and Methods: We analyzed samples of fifty patients with
Primary Antiphospholipid Syndrome (PAPS) and fifty healthy controls. Serum concentrations of IL-17, IL-23 and TGF-b were measured
by commercial ELISA kits. The SNP rs2275913 (IL17A), rs763780 (IL17F), rs11209026 (IL-23) and rs1800471 (TGFb) was genotyped using
commercial pre-synthesized TaqMan allelic discrimination assay.
Results and Conclusions: The levels of IL-17, IL-23 and TGF-b were significantly higher in PAPS patients than in the control group (p < 0.05,
Mann-Whitney test). No statistically significant differences were observed
in the distribution of genotypes and alleles of the rs2275913, rs763780,
rs11209026 and rs1800471 variants in patients with PAPS compared to
healthy subjects. Data from future association studies may be added to
the meta-analyses to obtain more precise estimates of effect sizes.
References
1 Jimenez S., Tassies D., Espinosa G., Garcia-Criado A., Plaza J.,
Monteagudo J., Cervera R., Reverter J.C.. Double heterozygosity
polymorphisms for platelet glycoproteins Ia/IIa and IIb/IIIa
increases arterial thrombosis and arteriosclerosis in patients with
the antiphospholipid syndrome or with systemic lupus erythematosus. Ann Rheum Dis 2008; 67: 835840.
2 Popovic-Kuzmanovic
D, Novakovic
I, Stojanovich
L,
Aksentijevich I, Zogovic N, Tovilovic G, Trajkovic V. Increased
activity of interleukin-23/interleukin-17 cytokine axis in primary antiphospholipid syndrome. Immunobiology 2013 Feb; 218(218691.
3 Horita T., Merrill J.T.. Genetics of antiphospholipid syndrome.
Curr Rheumatol Rep 2004; 6: 458462.
Lupus
457
A021
A022
MICRO-RNA NETWORK ANALYSIS IN LUPUS NEPHRITIS

IDENTIFIES SEVERAL BIOLOGIC PROCESSES INVOLVED IN
ITS PATHOGENESIS
Banos A.1,3, Krasoudaki E.1, Papagianni E.2, Stagakis I.1, Frangou E.3,
Cristofides A.3, Bertsias G.1, Iliopoulos D.4 and Boumpas D.T.1,3
1
Laboratory of Autoimmunity & Inflammation, IMBB, Heraklion,
Greece 2Department of Nephrology, Aristotle University of Thessaloniki,
Thessaloniki, Greece 3Laboratory of Inflammation and Autoimmunity,
BRFAA and Medical School, National and Kapodestrian University of
Athens, Athens, Greece 4Division of Digestive Diseases, UCLA, USA
Introduction: Gene expression represents the intermediate phenotype
between DNA and disease phenotypic variation, and provides insights
regarding genetic and epigenetic effects. MicroRNAs (miRNAs) regulate
the expression of genes involved in immune activation and response of the
kidney to the immune injury. We have performed miRNA analysis in the
peripheral blood and kidneys of patients with lupus nephritis (LN).
Aim: To identify miRNA-mediated gene expression and gene networks
involved in LN.
Methods: LN biopsies and peripheral blood mononuclear cells were
analyzed for expression level of human set of miRNAs, with a specifically designed array. Results identified differential expression of a list
of miRNAs between healthy and patient samples. We sum up the gene
targets of these miRNAs through Targetscan algorithm and proceed
with gene network analysis. We analyzed gene ontology for each set of
miRNA targets as well as their participation in major biological pathways, gene networks and disease signatures, using GeneCoDis and
Ingenuity Pathway Analysis, respectively. We also compared miRNA
levels between renal biopsies and the peripheral blood.
Results: In LN, several miRNAs presented with altered expression in renal
biopsies. Top upregulated miRNA is miR-422a, which regulates KLK4
gene. Another miR, miR-21 is a common genetic regulator both in renal
biopsies and the peripheral blood, though with discrete role in each tissue.
miRNA target genes identified in LN participate in networks associated
with renal failure, TGF-b signaling, multiple kinases (ERK, MAPK),
lupus pathogenesis, cytokine signaling and transcription. Validation of
these findings and identification of molecular biomarkers of LN and
lupus molecular signature are in progress.
Conclusion: Various miRNAs and their targets are key players in gene
networks that contribute to LN. Combination of this analysis with
miRNA regulation in blood may lead to identification of novel lupus
biomarkers.
TRANS-ANCESTRAL IMMUNOCHIP STUDY TO UNRAVEL

GENETIC RISK IN SLE
Cunninghame Graham D.1, Kelly J.2, Langefeld C.3, the SLE
ImmunoChip Consortium, Graham R.4, Gaffney P.2 and Vyse T.1
1
Kings College, London, 2Oklahoma Medical Research Foundation, OA
3
Wake Forest University, NC, 4Genentech Inc, CA
Introduction: Systemic lupus erythematosus (SLE) is the prototypic
autoimmune disease, with prevalence varying by ethnicity. The
strong genetic contribution to disease includes risk loci shared with
other autoimmune disorders.
Aim: To identify novel susceptibility loci for SLE and discover molecular
processes for disease we undertook a trans-ancestral association analyses
and pathway analysis on the Immunochip1 in four different ethnicities.
Patients and Methods: SLE cases met the American College of
Rheumatology criteria. In total 12147 cases and 16732 controls were
genotyped and passed quality control (Table 1). Association was modelled using a logistic regression adjusting for admixture proportions.
Trans-racial non-parametric meta-analysis was computed using
METAL. In each ancestry functional pathways were investigated
using GSA-SNP2. False discovery rate (FDR) adjusted p-values were
computed to account for the actual number of tests.
Results: Numerous regions met Immunochip-wide significance
(P<1x10-6) and PFDR<0.05 (Table 1). Top novel associations include
the transcription factor PHTF1, the RNA Polymerase II Associated
Protein RPAP2, the histone methyltransferase ASH1L (ASH1-Like
Protein), the receptor tyrosine kinase EFNA1/TNFAIP4, the inner
mitochondrial translocase TIMMDC1 and the secreted cytokine, CTF1.
Conclusion: Trans-ancestral mapping of known autoimmune loci has
revealed novel SLE-associated loci and signalling pathways important
in immunological function, which further extend our understanding of
the pathogenesis of lupus.
Table 1.
Ethnicity
AA
AsA
EA
HA
(ncase2970, (ncase557, (ncase6748, (ncase1872,
ncont2452) ncont748) ncont11516) ncont2016)
Number
P<1x10-6
7
of regions PFDR<0.05 27
6
22
35
35*
13
14
PFDR<0.001
Preliminary pathway analysis also revealed an enrichment of risk loci implicated in natural killer cell cytoxicity and in cell adhesion (Pcorrected<0.01 in
all four ethnicities) (Table 2).
Table 2.
Pcorrected for
KEGG Pathway
Ethnicity
AA
AsA
EA
HA
NK cytotoxicity
Cell adhesion
4.5x10-5
3.7x10-6
0.01
1.4x10-5
2x10-3
0.01
0.02
2x10-4
References
1 Brown and Cortes (2011) Arthritis.Res.Ther 13: 101103.
2 Kim et. al (2010) Nucleic.Acids.Res 38:W90-95.
Lupus
458
A023
TRANSCRIPTOMIC ANALYSIS REVEALS DECREASED
EXPRESSION OF KALLIKREIN-4 IN LUPUS NEPHRITIS DUE
TO UPREGULATION OF MICRO-RNA-422A
Krasoudaki E.1, Bertsias G.1, Stagakis E.1, Loupasakis K.2,
Zaboulaki A.1, Papagianni A.3, Alexopoulos E.3, Drakos E.4,
Iliopoulos D.2 and Boumpas D.T.1,5
1
Laboratory of Autoimmunity and Inflammation, Institute of Molecular
Biology-Biotechnology, FORTH, Greece 2Division of Digestive
Diseases, UCLA, USA 3Department of Nephrology, Aristotle University
of Thessaloniki, Thessaloniki, Greece 4Department of Histology,
University Of Crete, Greece 5University of Athens, Greece
Introduction: Lupus etiopathogenesis involves aberrancies in gene expression and function in immune effector cells and in target organs. We have
previously performed micro-RNA analysis in the peripheral blood to
reveal molecular pathways contributing to T-cell hyperactivity in lupus.
Aim: To analyze the micro-RNA transcriptome in lupus nephritis (LN)
and identify novel genes implicated in its pathogenesis.
Patients and Methods: RNA was purified from kidney biopsies of LN
patients (n7 proliferative, n5 membranous) and unaffected tissue
from renal carcinoma patients (n5). Micro-RNA expression was analyzed by TaqMan Low Density Arrays v1.0. Predicted gene-targets
identified by bioinformatics were validated by transfection studies
(luciferase assay, real-time PCR). Results were confirmed in the
NZB/NZW murine model of LN and protein expression was assessed
by immunoblotting and immunohistochemistry.
Results: Nine micro-RNAs were upregulated and 15 micro-RNAs were
downregulated in LN compared to control renal tissue. miR-422a
showed the highest upregulation (17-fold) and was found to target
kallikrein-4 (KLK4) in luciferase assay. In HEK-293T cells, overexpression of miR-422a suppressed KLK4 mRNA by 82%, whereas
KLK4 was increased in cells transfected with miR-422a inhibitor. In
line with the human data, miR-422a levels were increased and KLK4
mRNA levels were reduced in the kidneys of NZB/NZW LN mice.
These results were confirmed at protein level, and immunohistochemistry showed reduced KLK4 expression in the glomerular podocytes
and tubular epithelial cells in human and murine LN.
Conclusion: KLK4, a secreted serine esterase with angiogenic and extracellular matrix remodeling properties, may be downregulated by miR422a in LN. These data reiterate the involvement of local factors within
the kidney in determining the disease phenotype in lupus nephritis.
Epidemiology and outcomes - Registries and

cohorts - Environmental exposures
Patients and methods: In 2001 226 FDRs to a population-based lupus

cohort were examined for prevalence of autoantibodies and selfreported health (4). In 2013 a re-examination was performed.
Results: 193 out of 226 (85%) FDRs were alive and 143 (74%) participated. Participants and non-participants were comparable in all baseline characteristics. Deceased participants were older and with a male
preponderance but no difference in antinuclear antibody (ANA) status
was observed.
At baseline, significantly more FDRs were ANA positive in all titres,
compared to 200 healthy controls.
At follow-up the proportion of ANA positive FDRs had increased. Of
the 13 ANA positive at titer 1:160 at baseline, who participated in the
follow-up study, 9 (69%) were ANA positive at titer 1:160 and 1 (8%)
at titer 1:80 at follow-up. Except from ANA and Immunoglobulin M
Rheumatoid factor, no antibody or self-reported health complain at
baseline could convincingly predict antibody status or self-reported
health complaints at follow-up.
One participant developed SLE during follow-up. Nine reported to
have Rheumatoid Arthritis and six reported to have other connective
tissue diseases during follow-up.
Conclusion: The study underscores that FDRs to SLE patients have an
increased ANA prevalence compared to healthy controls and the
prevalence increases during 12 years follow-up.
The results show, that autoantibody positivity is a permanent phenomenon in certain relatives to SLE patients, especially those with high
ANA titers. To our knowledge this is the first study, where antibody
statuses of FDRs to SLE patients are followed over time.
References
1 Arbuckle MR, McClain MT, Rubertone M V, Scofield RH,
Dennis GJ, James J a, et al. Development of autoantibodies
before the clinical onset of systemic lupus erythematosus. The
New England journal of medicine [Internet]. 2003 Oct
16;349(16):152633.
2 Cardenas-Roldan J, Rojas-Villarraga A, Anaya J-M. How do autoimmune diseases cluster in families? A systematic review and metaanalysis. BMC medicine [Internet]. BioMed Central Ltd; 2013 Jan
[cited 2013 Aug 9];11.
3 Somers EC, Antonsen S, Pedersen L, Srensen HT. Parental
history of lupus and rheumatoid arthritis and risk in offspring
in a nationwide cohort study: does sex matter? Annals of the
rheumatic diseases [Internet]. 2013 Apr [cited 2013 Sep
24];72(4):5259.
4 Laustrup H, Heegaard NHH, Voss A, Green A, Lillevang ST,
Junker P. Autoantibodies and self-reported health complaints in
relatives of systemic lupus erythematosus patients: a community
based approach. Lupus [Internet]. 2004 Jan;13:7929.
A025
A024
A STUDY OF AUTOANTIBODIES AND SELF-REPORTED
HEALTH DURING 12 YEARS FOLLOW-UP IN RELATIVES TO
SLE PATIENTS
Langkilde H., Laustrup H. and Voss A.
Department of Rheumatology, Odense University Hospital, Denmark
Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune
disease characterized by presence of autoantibodies and characteristic
multiorgan involvement. Autoantibodies may evolve years before SLE
diagnosis (1). First degree relatives (FDR) to SLE patients have a
higher prevalence of autoantibodies and are more prone to suffer
from autoimmune and rheumatic diseases (2,3).
Aim: To study, if previous autoantibodies and self-reported health
complaints can predict autoantibody status and self-reported health
complaints at follow-up.
ASSESSMENT OF DAMAGE ACCRUAL AND

SOCIOECONOMIC STATUS IN A LARGE INTERNATIONAL
SLE COHORT
Pamfil C.1, Furtunescu F.2, Perna A.3, Mihalcea S.4, Leszczynski P.5,
Majdan M.6, Kiss E.7 and Rednic S.1
1
Iuliu Hatieganu University, Cluj-Napoca, Romania 2Carol Davila
University, Bucharest, Romania 3GSK, London, UK 4GSK, Bucharest,
Romania 5Poznan Medical University, Poland 6Medical University of
Lublin, Poland 7National Institute of Rheumatology and Physiology,
Budapest, Hungary
Introduction: Assessment of organ damage has become the standard
outcome measure for morbidity and mortality in patients with systemic
lupus erythematosus (SLE).
Aim: Determine the extent of damage accrual, identify associated variables, and assess socioeconomic status of patients with SLE.
Lupus
459
Patients and methods: The SESAME study was a prospective, observational study. Consecutive SLE patients (N737) were enrolled at 19
specialized lupus centers (Romania11, Poland6, Hungary2) and
followed-up for 12 months. Disease damage and activity were assessed
by SLICC Damage Index (SDI) and SELENA-SLEDAI. Here we
report data gathered at patient inclusion.
Results: Mean standard deviation age at SLE diagnosis and disease
duration were 33.9 12.9 years and 8.0 7.7 years, respectively.
Compared to patients with SDI0 (n384), patients with SDI1
(n353) had longer disease duration (p<0.001), higher proportion
of disability (p<0.001), higher proportion of medical retirement
(p0.045), lower proportion of employment (p<0.001), higher proportion of financial support and social assistance (p<0.001), and
were more likely to require inpatient hospitalization (39% vs 54%,
p<0.004). The highest frequencies within the items of SDI were recorded for patients with glucocorticoid-related/potentially-related
damage, deforming/erosive arthritis and scaring chronic alopecia.
Patients with SDI1 also had higher disease activity (p<0.001) and
a higher median dose of glucocorticoids than patients with SDI0 (10
vs 7.5 mg/day; p0.004). The damage accrual group had a significantly
lower proportion of subjects with anti-Ro antibodies (p0.018), and a
similar proportion of subjects receiving antimalarial therapy.
Conclusion: Damage accrual was associated with disease activity and
duration, glucocorticoid dose, disability and a more vulnerable socioeconomic status. These initial SESAME findings highlight the need to
reduce damage accrual, for patients and socioeconomic reasons, by
controlling disease activity and minimising reliance on corticosteroids.
university Hospital as well as from smaller nephrology units in secondary care hospitals. Demographic, clinical and histological features were
recorded.
Results: From a total of 768 biopsies, we identified 63 (8.2%) cases of
lupus nephritis, corresponding to a prevalence of 17 per 100,000 in the
general adult population in Crete. Since the prevalence of SLE in Crete
is 123 per 100,000, this corresponds to 14% lupus patients having
biopsy-proven nephritis. The mean age at the time of lupus nephritis
diagnosis was 31.7 years (28.9 years in men, 32.0 years in women) with
female:male ratio of 5.3:1. In 41% of the cases, nephritis was the presenting manifestation of lupus, whereas in the remaining 59% kidney
biopsy was performed during the course of the disease. Average activity index was 5.4 and chronicity index was 1.9. Histological findings
compared with gender are shown in the figure below. Further analyses
are underway to determine long-term renal and patient outcomes in
association with sociodemographic characteristics and the type and
responses of administered therapies.
Reference
1 Gladman DD, et al. J Rheumatol. 2003;30:1955-9.
A026
BIOPSY-PROVEN LUPUS NEPHRITIS IN A SOUTHERN
EUROPEAN GENETICALLY HOMOGENOUS POPULATION
Tzanakakis M.1, Gergianaki I.2,3, Xydakis D.4, Papadaki A.5,
Perysinaki G.6, Petra X.1, Maragaki E.1, Stratakis S.1, Poulidaki R.1,
Perakis K.1, Vardaki E.1, Stratigis S.1, Stylianou K.1, Nakopoulou L.7,
Gakiopoulou X.7, Sotsiou F.8, Fanouriakis A.2, Bertsias G.2,3,
Ntaountaki E.6, Parasiris G.6, Papadogiannakis A.4, Tzanakis G.5,
Boumpas D.T.3,9, Sidiropoulos E.2 and Dafnis E.1
1
Nephrology Department, University of Crete, Heraklion, Greece;
2
Rheumatology, Clinical Immunology and Allergy, University of Crete,
Heraklion, Greece; 3Institute of Molecular Biology-Biotechnology,
FORTH, Greece; 4Nephrology Department, Venizeleio General
Hospital, Heraklion, Greece; 5Nephrology Department, General
Hospital of Chania, Greece; 6Nephrology Department, General Hospital
of Rethymnon, Greece; 7Pathology Department, Medical School,
University of Athens, Athens, Greece; 8Pathology Department,
Evaggelismos Hospital, Athens, Greece; 9University of Athens, Athens,
Greece; deceased
Introduction: Renal involvement is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. The frequency, severity and outcome of lupus nephritis differs according to patient
demographic characteristics such as race, gender, and age and between
populations from different countries. Importantly, studies in major academic, inner city, tertiary referral centers are prone to referral biases.
Aim: To determine the profile of lupus nephritis in a genetically homogenous population with shared environmental exposures living in both rural
and urban settings, and to identify factors affecting renal survival.
Patients and Methods: We reviewed retrospectively the histological
diagnosis of all renal biopsies performed on residents of the island
of Crete (population approximately 0.6 million) during the years
1991-2013. Cases of lupus nephritis were identified from both the
Conclusions: Biopsy-proven lupus nephritis may be less common than

previously reported by major academic centers.
A027
CARDIOVASCULAR RISK ASSESSMENT IN A SLE COHORT
WHERE DO WE STAND?
Canico J., Meirinhos T., Aguiar T., Ambrosio C. and Barcelos A.
RheumatologyDepartment Centro Hospitalar do Baixo Vouga E.P.E.Aveiro, Portugal
Introduction: The pathogenesis of cardiovascular risk in
SystemicErythematosus Lupus (SLE) is the result of a complex interaction between traditional risk factors, disease specific factors and
chronic inflammation. To minimize de cardiovascular risk in these
patients, doctors should control every risk as possible, to avoid an
increase in the mortality and morbidity.
Objective:In order to implement afollow-up protocol in our SLE
patients, the authors made a transversal assessment on cardiovascular
risk factors, and how they are controlled, or not, in a SLE cohort.
Methods: A convenient sample of outpatients with SLE attending our
Rheumatology Clinic was recruited. Clinical and laboratorial data
were collected using the hospital information records. Statistical analysis was performed using Excel.
Results: 60 patients were enrolled (54 women and 6 men), with a mean
age of 41,1years and a mean disease duration of 7,4 years. 13 patients
had smoking habits and 22 patients were overweight, but there were no
available data of the weigh or height of 21 patients. 12 patients had a
blood pressure superior to 130/80 mmHg. Only 5 patients were insulin
resistant,none was diabetic. Mean creatinine was 0,81 mg/dl and albumin 3,9 g/dl. 25 patients had proteinuria >300mg /24 hours. Mean Creactive protein was 0,73 mg/dl. Concerning cholesterol levels in this
SLE patients cohort: 21 had LDH>100 mg/dl, 12 total
Lupus
460
cholesterol>200 mg/dl, 7 HDL< 40 mg/dl and 5 had triglycerides>150 mg/dl.7 patients had no lipid profile in the last year.
12 patients were medicated with statins and 28 with angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The mean
dose of corticosteroid was 5,6 mg pd.
In this SLE cohort, there were 8 thrombotic vascular events but 5 of
these patients had also antiphospholipid syndrome.
Conclusion: The results reinforce the importance of a protocolled followup that couldavoid the lack of some important clinical and laboratorial
data and a better/more efficient control of co-morbidities in SLE patients.
A028
CEREBRAL EVENTS IN SYSTEMIC LUPUS
ERYTHEMATOSUS PATIENTS WITH ANTIPHOSPHOLIPID
ANTIBODIES: RESULTS FROM THE SERBIAN NATIONAL
COHORT STUDY
Stojanovich L.1, Djokovic A.1, Damjanov N.2, Marisavljevic D.1 and
Smiljanich-Miljkovich D.3
1
Internal medicine, Bezhanijska Kosa University Medical Center,
Belgrade, Serbia 2Institutut of Rheumatology Belgrade University,
Serbia 3Hospital Center Zemun, Department of Neurology, Belgrade,
Serbia
Introduction: Central nervous system involvement is one of the most
prominent clinical manifestations in patients with systemic lupus
erythemathosus (SLE) as well as in antiphospholipid syndrome
(APS) and includes thrombotic events, psychiatric features and a variety of other cerebral syndromes.
Objectives: Demonstration of the cerebral events in patients with SLE
from the Serbian National APS Registry.
Patients and methods: We analyzed 142 SLE patients with secondary
APSaAPS (90.8% female and 9.2% male) average age 47.214.8
years. Antiphospholipid antibodies (aPL) analysis included analysis
of aCL (IgG/IgM), 2GPI (IgG/IgM) and LA. Diagnosis of neurological manifestations was established by clinical findings. In addition
to neurologic and psychiatric examination, the CNS involvement was
assessed with digital electroencephalography, visual, somatosensory,
and acoustic evoked potentials, electromyoneurography, and MRI.
Results: Overall neurological and psychiatric manifestations were present in 77.9% sAPS patients. Transitient ischemic attack in 28.2%,
stroke in 28.9%, chorea in 7.0%, hemiballismus in 0.7% cerebellar
ataxia in 0.7%, epilepsy in 18.3%, migraine in 29.6%, transient
global amnesia in 2.8%, multiinfarct dementia in 13.4% acute ischemic
encephalopathy in 7.9%, anterior spinal artery syndrome in 0.7%.
57.9% sAPS patients had aCL-IgG positive; 61.4% patients had
aCL-IgM positive; 40.7% patients had b2GPI IgG positive, 45.0%
patients had b2GPI IgM positive; and 51.1% were LA positive. We
revealed positive relationship between aCL IgG and incidence of acute
ischemic encephalopathy (p0.02), aCL IgM and epilepsy (p0.04)
and 2GPI IgG and stroke (p0.008). There was no positive correlation between others aPL and neurological manifestations.
Conclusions: The Serbian National APS Registry allowed us to ascertain a significantly increased incidence for the certain neurological
manifestations in SLE patients with sAPS. All tipes of aFL are specific
to detect SLE patients at risk for the cerebral events.
Acknowledgements: This work was supported by research grant
number 175041 for 2011-2014, issued by the Ministry of Science of
the Republic of Serbia.
References
1 Arnson Y, Shoenfeld Y, Alon E, Amital H. The Antiphospholipid
Syndrome as a Neurological Disease. Seminars in Arthritis and
Rheumatism 2010; 40: 97108.
2 Roldan JF, Brey RL. Neurologic manifestations of the antiphospholipid syndrome. Curr Rheumatol Rep 2007; 9: 10915.
3 Stojanovich L, Zadman-Goddard G, Pavlovich S, Sikanich N.

Psychiatric manifestations in systemic lupus erythematosus.
Autoimmun Rev 2007; 6: 42126.
4 Stojanovich L, Kontic M, Smiljanic D, Djokovic A, Stamenkovic
B, Marisavljevic D. Association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipid
syndrome. Clin Exp Rheumatol 2013; 31(5756760.
A029
CHARACTERISTICS, NEEDS AND SOURCES OF
INFORMATION OF A FRENCH ONLINE COMMUNITY OF
SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS
Meunier B.1, Harle J.-R.1, Chekroun M.2 and Chiche L.1
1
La Conception hospital, department of internal medicine, Aix-Marseille
University, Marseilles, France 2Carenity, Paris, Franc
Introduction: There is a lack of data about needs and sources of information of patients with rare diseases. Internet forums are understudied
resources to know more about living with such diseases. Carenity is the
first French online platform allowing peer-to-peer exchanges, within
online communities dedicated to specific diseases, including Systemic
Lupus Erythematosus (SLE).
Aim: Describe characteristics of the Carenity SLE community and
identify needs and sources of information of SLE patients.
Patients and Methods: One year after creation of the SLE community,
all the posts were analyzed. A focused cross-sectional online survey
was also proposed to members of the community.
Results: The SLE community included 521 people (female:93%; mean
age:38.9 years) geographically distributed homogeneously throughout territory. From a total of 6702 posts, 2232 could be classified into specific
topics. The 10 most popular topics (836 posts) were Lupus and [. . .]:
treatment, fatigue, entourage, sun exposure, diagnosis, autoimmune diseases, pregnancy, contraception, symptoms and sexuality. Additional
topics of interest (with at least 10 posts each) were Lupus and [. . .]:nutrition, physical activity, work, weight, psychological impact, toxics, vaccines,
fibromyalgia, global management, outcomes, paraclinical investigations.
From April to May 2013, 112 patients fulfilled the online survey. They
reported lack of information about: 1)At diagnosis: outcome, treatments,
daily life, patient associations, symptoms, disease, psychosocial aspects;
2)At treatment initiation: side effects, long-term effects, duration/cessation,
type, mechanism of action. Sources of information were various with relative variations according to timing respectively just before, just after
diagnosis and before treatment initiation: healthcare providers (51/61/
67%), journals/magazines (7/12/6%), patient associations (11/23/9%),
lupus websites (51/77/40%), web forums/blogs (34/53/19%). Internet was
used to find information about SLE via search engines(74%), health portals(55%), forums(46%), patients associations websites(46%), French
patients blogs(31%), Facebook(21%).
Conclusion: This study provides relevant data on the needs and sources
of information of SLE patients which could be used to improve content and form to provide more relevant information.
A030
CHRONIC DAMAGE IN SLE PATIENTS: RESULTS FROM A
LARGE MONOCENTRIC COHORT
Ceccarelli F., Massaro L., Perricone C., Leccese I., Truglia S.,
Miranda F., Alessandri C., Spinelli F.R., Conti F. and Valesini G.
Lupus Clinic, Rheumatology, Sapienza Unversity, Rome
Introduction: Published data suggest a significantly higher mortality in
patients affected by Systemic Lupus Erythematosus (SLE) developing
chronic damage. Therefore, to prevent damage is a major goal in the
management of SLE patients.
Lupus
461
Aim: We assessed chronic damage by means of the SLICC Damage
Index (SDI), in a large monocentric Italian cohort of SLE patients and
we aimed at evaluating its associations with demographic factors, clinical features, disease activity and laboratory findings (1).
Patients and Methods: We enrolled patients affected by SLE according
with ACR 1997 criteria. Chronic damage was retrospectively determined by SDI at the last visit in all the patients with at least 6
months of follow-up. Disease activity was assessed by the SLEDAI2K and flare was defined as an increase of SLEDAI-2K4 compared
with previous visit.
Results: We enrolled 349 SLE patients (M/F 25/324, mean ageSD
42.712.4 years, mean disease durationSD 164.9105.2 months):
125 patients (35.8%) showed a SDI1 (meanSD 1.70.9, range 05). The musculoskeletal was the most frequently involved system (41/
125 patients, 32.8%), with development of deforming/erosive arthritis
in 21 subjects. The presence of chronic damage was associated with
significantly higher age (P<0.001), disease duration (P<0.001),
number of flares (P0.02), and with the use of glucocorticoids
(P0.02). The logistic regression analysis revealed the association
between the neuropsychiatric damage and the presence of antiphospholipid syndrome (P0.01, OR3.9) and between the presence of
cardiovascular damage and positive test for anti- b2GPI antibodies
(P0.01, OR 6.2).
Conclusions: In our large SLE population we identified a mild chronic
damage in 36% of evaluated patients. The association with the number
of flares confirms the need to control disease activity in order to prevent the damage. Finally, the possible role of antiphopholipid antibodies (aPL) in the development of cardiovascular and neurological
damage may suggest a tight-control in aPL positive patients.
References
1 Gladman D, J Rheumatol. 1992.
A031
DAMAGE PREDICTORS IN PATIENTS FROM THE
PORTUGUESE LUPUS REGISTRY
Goncalves M.J.1,3, Sousa S.2, Ines L.S.4, Duarte C.4, Borges J.5,
Silva C.5, Romao V.C.1,3, Terroso G.6, Bernardes M.6, Cerqueira M.7,
Raposo A.7, Sequeira G.8, Barcelos A.9, Canas da Silva J.1, Costa L.6,
Pereira da Silva J.A.2, Miranda L.5, Silva J.A.P.4, Canhao H.1,3 and
Santos M.J.2,3
1
Hospital de Santa Maria, Lisboa 2Hospital Garcia de Orta, Almada
3
Rheumatology Research Unit, Instituto Medicina Molecular, Lisboa
4
Hospitais da Universidade de Coimbra, Coimbra 5Instituto Portugues
Reumatologia, Lisboa 6Hospital de Sao Joao, Porto 7Hospital Conde de
Bertiandos, Ponte de Lima 8Hospital de Faro, Faro 9Hospital de Aveiro,
Aveiro, Portugal
Introduction: Systemic lupus erythematosus (SLE) survival rate has
improved dramatically. However, many patients develop irreversible
organ consequences during the course of disease. The SLICC/ACR
damage index (SDI) measures cumulative damage and is associated
with a higher morbidity and mortality rate.
Aim: Characterization of damage and identification of damage
predictors.
Patients and Methods: SLE patients from the Portuguese register
Reuma.pt/LES and available SDI were included. A cross sectional
analysis was made upon records of the last visit. Predictor factors
for damage, defined as SDI 1, were determined by a multivariate
logistical regression model.
Results: 1099 patients were studied (439 with SDI 1), mean SDI score
was 0.741.26. Musculoskeletal (24.6%), neuropsychiatric (23.0%)
and ocular (16.4%) domains were the most commonly affected.
Patients with damage were significantly older, had longer disease
duration and later disease onset. Black ethnicity, discoid rash, serositis,
renal and neuropsychiatric involvement associated positively with
SDI1. Hypertension, antiphospholipid syndrome and Sjogrens syndrome were also more prevalent in this group. The use of antimalarials
(ever or current) showed a negative association with damage. In multivariate analysis, age, disease duration, renal involvement, serositis, discoid rash and positivity of anti-phospholipids were predictors of
damage. Gender and SLEDAI score at last visit were not associated
with damage.
Conclusions: In this large cohort study, clinical and demographic characteristics were found to be associated with damage. Patients with
SDI1 have different clinical manifestations, older age and longer disease duration. Our nationwide study provides crucial information on
damage in a homogenous South European SLE population.
A032
HEALTH-RELATED QUALITY OF LIFE IN SERBIAN LUPUS
FEMALE PATIENTS USING SF-36 AND SLEQOL
Stojkovic S.1, Vrbavac M.2 and Stojanovic R.3,4
1
Special Hospital for Rheumatic Diseases Novi Sad, Novi Sad, Serbia
2
General Hospital Loznica, Loznica, Serbia 3Institute of Rheumatology
Belgrade 4University of Belgrade School of Medicine, Belgrade, Serbia
Introduction: The Medical Outcomes Study Short Form-36 (SF-36) is
the most common generic instrument used to measure quality of life in
Systemic Lupus Erythematosus (SLE), while the Systemic Lupus
Erythematosus Quality of Life (SLEQoL) questionnaire is disease-specific for adults with SLE.
Aim: To investigate the association of SF-36 and SLEQoL measurements in SLE patients.
Patients and Methods: The cross-sectional study included 50 female
SLE patients, average age of 43.3211.58 (range 22-63), treated at
the Institute of Rheumatology in Belgrade. Health-related quality of
life (HRQoL) was assessed by applying the SF-36 and SLEQoL.
Descriptive statistics, and the Chi-square test and Pearson0 s correlation
coefficient were used.
Results: Within SF-36, the Mental Component Summary (MCS) score
was better than the Physical Component Summary (PCS) score. The
best quality of life was shown in the domains of Vitality (VT) and
Bodily Pain (BP), whereas the Role limitations caused by Physical
problems (RP) were perceived as the worst. Within SLEQoL, the
best quality of life was noted in the domain of Treatment, whereas
Self-image and Activity were perceived as the worst. The correlation
between the SF-36 PCS score and the SLEQoL score was r-0.666
(p<0.01). The correlation between the SF-36 MCS score and the
SLEQoL score was r-0.648 (p<0.01). In general, the SLEQoL
score had a better correlation with the SF-36 domains than the SF36 and SLEQoL domains had with each other. The correlation of
comparable domains ranged from strong to weak correlation, while
the SLEQoL Treatment wasnt comparable to any of the SF-36
domains.
Conclusions: Both SF-36 and SLEQoL were useful instruments in
assessing HRQoL in Serbian lupus female patients. It is prudent to
use both tests in order to minimize their limitations.
References
1 Leong KP, Kong KO, Thong BY, et al. Development and preliminary validation of a systemic lupus erythematosus-specific quality-of-life instrument (SLEQOL). Rheumatology (Oxford) 2005;
44(10126776.
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462
A033
HIGH EXTENT OF CORONARY ARTERY CALCIUM AMONG
DANISH PATIENTS WITH SYSTEMIC LUPUS
ERYTHEMATOSUS - A POPULATION-BASED STUDY
Kay S.D.1,3, Diederichsen A.C.2, Poulsen M.K.2, Diederichsen L.P1,
Laustrup H.1 and Voss A.1,3
1
Department of Rheumatology, Odense University Hospital, Denmark
2
Department of Cardiology, Odense University Hospital,
Denmark.3University of Southern Denmark
Introduction: Patients with systemic lupus erythematosus (SLE) have
an increased risk of cardiovascular disease (CVD), which has been
demonstrated to have major impact on morbidity and mortality.
This increased risk of CVD may be due to an increased prevalence
of atherosclerosis.
Aim: The aim of this study was to evaluate the prevalence and the
extent of coronary artery calcium among Danish patients with SLE
compared with healthy control subjects.
Patients and Methods: In a population-based predominantly Caucasian
cohort we recruited 84 SLE patients and 52 healthy controls. All subjects underwent a cardiac CT scan with assessment of the coronary
artery calcium score (CAC). Measurement of CACS was expressed in
Agaston units. Demographic and clinical characteristics were obtained
prospectively from study subjects. For SLE patients, duration of disease and SLICC were assessed.
Results: The SLE patients were 93% women, mean age 50.9 14.3
years. The controls were 67% women, mean age 57.0 11.5 years.
Median CACS did not differ between SLE patients and controls,
However, high CACS (>400) were more frequent among SLE patients
than controls (16% vs. 3%). CACS among SLE patients range from 09725, while among controls from 0-682.
In patients with SLE, high CACS (>400) were associated with age,
hypertension and waist-hip ratio, but also with SLICC.
After adjustment for age and sex, SLE patients had significantly higher
odds of having CS > 400 (OR17.25, 95% CI: 2.73-108.76, p
0.002).
Conclusion: In a population-based SLE cohort high extent of CACS
occur more frequent as compared with healthy controls. High CACS is
associated with age, hypertension and abdominal obesity, as well as
SLE damage.
References
1 Manzi S, et al. Age-specific Incidence Rates of Myocardial Infarction
and Angina in Women with Systemic Lupus Erythematosus:
Comparison with the Framingham Study. Am J Epidemiol 1997
Mar 1; 145(540815.
A034
LOWER PREVALENCE OF HEPATITIS B VIRUS INFECTION
BUT WITH POORER LIVER PROGNOSIS IN SYSTEMIC
LUPUS ERYTHEMATOSUS IN TAIWAN
Lin T.S. and Hsu P.N.
National Taiwan University Hospital, Division of Allergy, Immunology
and Rheumatology, Department of Internal Medicine, Taipei, Taiwan
Introduction: SLE patients are more suspesible to infection. It is a
concern for HBV reactivation in SLE patients. Prophylactic therapy
for HBV was recommended before immunosuppresant therapy.
However, there was only limited data about the prevelance of HBV
infection in SLE patients. The liver prognosis of HBV infection in SLE
patients is still not clear.
Aim: To clarify the prevalence and liver prognosis of HBV infection in
SLE patients.
Patients and Method: The medical records of SLE patients had ever
been hospitalized during 2011-2013 in National Taiwan University
Hospital were reviewed. All patients fulfilled the revised ACR criteria
for diagnosis of SLE. HBV infection was defined as positive HBs-Ag.
The prevalance of HBV infection was calculated. Person Chi-squre test
was used to evaluate the diffierence of the liver prognosis.
Results: A total 369 SLE patients were evaluated. HBs-Ag had been
tested in 279 patients. There were 24 HBs-Ag positive patients. The
prevalence of HBV infection in SLE patients was 8.7% (24/279).
Among the 24 patients, seven developed acute liver failure. There
were 5 patients died due to acute liver failure. In contrast, among
the SLE patients without HBV infection, no one developed acute
liver failure. There was significantly increased risk of aucte liver failure
in the HBV infection group (P < 0.05).
Conclusion: Ih this retrospective study, the prevalence of HBV infection in SLE patients was lower than the general polpulation in Taiwan
(8.7% v.s. 15-20%). However, the risk of acute liver failure in SLE
patients with HBV infection was much higher than those without HBV
infection. This study provides evidence that there is increased HBV
reactivation and with poor liver outcome in SLE patients. It also highlights the importance of prophylactic therapy in SLE patients with
HBV infection.
A035
MORTALITY PREDICTORS IN SERBIAN PATIENTS WITH
SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM A
SINGLE CENTER
Stojanovich L., Djokovic A. and Stanisavljevic N.
Bezhanijska Kosa University Medical Center, Belgrade, Serbia
Objective: To analyze risk factors for death outcome in SLE patients
followed prospectively in a single center.
Methods: The study included 244 patients with SLE followed over a 20year period according to a standard protocol at the University Center
Bezanijska kosa. Clinical and laboratory indicators of disease activity were recorded at each clinic visit and entered into a database.
Results: There were 226 (92.6%) women and 18 (17.4) men with
median age at the onset of disease of 45 years and mean SLEDAI
9.72. 48.3% of the pts had criteria for antiphospholipid syndrome.
Average disease duration was 7.317.07. Smoking was present in
29.2% pts, hypertension in 28.3%, dyslipidemia in 23.2%, obesities
in 20.2% pts, diabetes in 5.5%, and there were 37.6% postmenopausal
women. Total of 239 pts (98%) was treated with steroids, 33.5% with
cyclophosphamide and 98% of pts with antimalarics. 93.4% pts had
non-erosive arthritis, 80.7% photosensitivity, 66% hematologic disorder, neurologic disorder in 48.8%, serositis in 32.4%. Nephritis
was diagnosed in 25% of the cases. Mortality rate through 20-year
period was 11.1%. Thromboembolic event was cause of death in
33.3% cases, 22.2% had CAPS, and same percentage of patients
(11.1) died due sepsis and malignant diseases whereas in 7.4% cases
cause of death was SLE related or drug withdrawal. Mortality risk
factors were age 50 years (p0.002), renal damage (p0.003) and
serositis (0.024) as well as cigarette smoking (p0.002) and menopause
(p0.002).
Conclusion: Multi-organic involvement in older patients was associated
with higher mortality in Serbian SLE patients attended in a tertiary
care center.
References
1 Urowitz MB, Gladman DD, Abu-Shakra M, Farewell VT.
Mortality studies in systemic lupus erythematosus. Results from a
single center. III. Improved survival over 24 years. J Rheumatol
1997; 24: 10611065.
2 Moss KE, Ioannou Y, Sultan SM, Hag I, Isenberg DA. Outcome
of a cohort of 300 patients with systemic lupus erythematosus
Lupus
463
attending a dedicated clinic for over two decades. Ann Rheum Dis
2002; 61: 409413.
3 Funauchi M, Shimadzu H, Tamaki C, et al. Survival study by
organ disorders in 306 Japanese patients with systemic lupus erythematosus: Results from a single center. Rheumatol Int 2007; 27:
243249.
A036
OUTCOME OF SYSTEMIC LUPUS ERYTHEMATOSUS IN
IRAN
Fatemi A.1, Matinfar M.2, Maracy M.3, Sayedbonakdar Z.1, Saber M.4
and Smiley A.5
1
Department of Rheumatology, Isfahan University of Medical Sciences,
Isfahan, Iran 2Department of Internal Medicine, Isfahan University of
Medical Sciences, Isfahan, Iran 3Department of Biostatistics &
Epidemiology, Isfahan University of Medical Sciences, Isfahan, Iran
4
Department of Dermatology, Isfahan University of Medical Sciences,
Isfahan, Iran 5Isfahan, Iran
Introduction: No study about mortality in systemic lupus erythematosus (SLE) in Iran has been yet published in Pubmed.
Aim: This study was designed to determine the survival of SLE patients
and its predictors in Iran
Patients and Methods: 394 patients who were diagnosed with SLE and
admitted to our hospital between 1985 and 2011 were included in a
retrospective study. The patients baseline characteristics including the
clinical and laboratory manifestations recorded at the time of diagnosis
were reviewed. The patients were contacted to verify whether they are
alive or not. The causes of mortality were extracted as well. Relevant
factors of survival were explored through Cox regression analysis.
Results: Female/male ratio was 8.4%. 359 patients were alive at the end
of follow-up. Major organ involvement including lupus nephritis
(29%) and pulmonary hemorrhage (14%), infections (29%) and cardiovascular diseases (23%) were the main causes of death. 21.6 years
was the mean survival time. Its 95 % CI was 20.4-23 years. The overall
survival rate after 5.years was 93%. At the end of 10 and 15 years it
was similarly 90% whereas it dropped to 80% by 20 years. Older age at
onset ( 35 years), seizure, hematuria and pericarditis at the time SLE
diagnosis were significantly associated with death by univariate analysis. But, only pericarditis and seizure kept their significant effects on
survival after multivariate analysis.
Conclusion: Our study showed comparable survival rate of patients
with SLE in Iran to that in developed countries.
References
1 Kasitanon N, Magder LS, Petri M. Predictors of survival in systemic lupus erythematosus. Medicine 2006 May; 85(314756.
A037
PREMATURE DEATH IN SYSTEMIC LUPUS
ERYTHEMATOSUS MEASURED BY YEARS OF POTENTIAL
LIFE LOSS BEFORE 60 YEARS OF AGE. A POPULATION
BASED STUDY
Lerang K.1, Gilboe I. M.1, Thelle D. S.2 and Gran J. T.1,3
1
Department of Rheumatology, Oslo University Hospital,
Rikshospitalet, Oslo, Norway 2Department of biostatistics, Institute of
basic medical science, University of Oslo, Norway 3Institute of Clinical
Medicine, University of Oslo, Norway
Aim: To examine the rate and causes of premature death in a population-based cohort of Systemic Lupus Erythematosus (SLE), and to
compare these with the general population.
Patients and methods: Multiple sources were used to identify 325 SLE
patients within the city of Oslo during 1999-2009 who met 4 of the
American College of Rheumatology (ACR) criteria. The Years of

Potential Life Loss before 60 years of age (YPLL60) and causes of
death of these patients were examined and compared to a matched control population. The potential years of life lost (YPLL) was the sum of the
numerical difference between a predetermined end-point-age (defined as
60 years old) and the age at death for deaths that occurred prior to that
end point age. The YPLL (60) rate is found by dividing YPLL by years of
observation for the population under age 60. The analysis includes underlying, immediate and contributing causes of death.
Results: A total of 50 SLE patients died during the study period of
whom 20 were under 60 years of age. SLE patients had 259 years lost
and 2241 years of observation before 60 years of age (116/1000) and
the control population had 144 years lost and 11576 years of observation (12 /1000). The mean (SD) YPLL60 for females and males were 15
(11) and 8 (4) (p0.08) and for patients with and without lupus nephritis 21 (10) and 8 (6) (p0.01) Figure 1 rank the attribution of causes
of death in SLE in consecutive order.
Conclusion: The study found an increased YPLL60 in SLE. Women
and patients with kidney involvement lost on average 15 and 21 years
respectively. We believe the YPLL measurements supplements traditional methods of measuring mortality.
Figure 3 Annual years of potential life loss before 60 years of age
(YPLL60) related to specific causes of death per 1000 SLE patients
and their control subjects (matched for sex, age and ethnicity). Active
SLE disease is registered from medical record.
CVD; Cardiovascular disease, CNS; Central nervous system.

A038
REUMA.PT/LES: THE PORTUGUESE LUPUS REGISTER
Sousa S.1, Goncalves M.J.2,3, Ines L.S.4, Duarte C.4, Fernandes S.5,
Silva C.5, Romao V.C.2,3, Terroso G.6, Bernardes M.6, Cerqueira M.7,
Raposo A.7, Sequeira G.8, Barcelos A.9, Canas da Silva J.1, Costa L.6,
Pereira da Silva J.A2, Miranda L.5, Silva J.A.P.4, Canhao H.2,3 and
Santos M.J.1,3
1
Hospital Garcia de Orta, Almada; 2Hospital de Santa Maria, Lisboa;
3
Rheumatology Research Unit, Instituto de Medicina Molecular, Lisboa
4
Hospitais da Universidade de Coimbra, Coimbra 5Instituto Portugues
de Reumatologia, Lisboa 6Hospital de Sao Joao, Porto 7Hospital Conde
de Bertiandos, Ponte de Lima 8Hospital de Faro, Faro 9Hospital de
Aveiro, Aveiro. Portugal
Introduction: The Rheumatic Diseases Register from the Portuguese
Society of Rheumatology has expanded its coverage to Systemic
Lupus Erythematosus (SLE) - Reuma.pt/LES. It is a web-based platform launched in September 2012 that simultaneously serves as a
nationwide registry and as an electronic medical record. Its aim is to
register all patients with SLE and follow them up in a standard manner
in order to improve the monitoring and clinical care for patients with
SLE while increasing the knowledge of this disease.
Aim: Characterization of the SLE Portuguese population included in
Reuma.pt/LES
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464
Patients and methods: SLE patients registered in the Reuma.pt/LES
until December 2013 are described.
Results: 1510 patients were included. The majority (92%) are women
with an average age of 47.714.9 years. 94.5% are Caucasian, 4.6%
black and 0.9% of other races. The mean disease duration was
13.88.9 years and the most prevalent manifestations were mucocutaneous, hematological and musculoskeletal. Co-morbid conditions were
recorded in 641 patients, being the most frequent hypertension
(31.5%), thyroid diseases (10.8%) and diabetes (7.2%). Secondary
Sjogren syndrome and antiphospholipid syndrome were documented
in 10.6% and 7.6% of patients, respectively. SLEDAI-2K at last visit
was in average 2.533.18. SLICC/ACR damage index was in average
0.71.23. About 50% of the patients were ever treated with corticosteroids and 63.3% with antimalarials.
Conclusions: Reuma.pt is a very useful tool that allows a more efficient
patient follow-up, and standardized data collection and analysis, with
the ultimate objective of improving patient care and simultaneously
scientific research in the field of SLE.
A039
SURVIVAL ANALYSIS AND CAUSES OF MORTALITY AMONG
INPATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN
A ROMANIAN TERTIARY CARE HOSPITAL OVER 20 YEARS
Pamfil C.1, Stroe I.2, Flestea A.3, Popov I.2, Rinzis M.2, Candrea E.1,
Damian L.2, Felea I.2, Zdrenghea M.1 and Rednic S.1
1
Iuliu Hatieganu University, Cluj 2Emergency Clinical County Hospital,
Cluj 3Babes-Bolyai University, Cluj, Romania
Introduction: Despite progress in management, mortality in systemic
lupus erythematosus (SLE) is still high.
Aim: We investigated the causes of death, clinical determinants of survival and survival rates in a longitudinal cohort of hospitalized SLE
patients.
Patients and Methods: Demographic data, cumulative clinical features,
disease activity and damage scores were analysed in 117 SLE patients
followed-up between 1990 and 2013. Causes of death were defined on
the basis of clinical data and, when available, postmortem examination. Survival rates were calculated by the Kaplan-Meier method
and log-rank test.
Results: A total of 15 (80% female) out of 117 patients died; SLErelated deaths were the main cause of demise (40%), followed by catastrophic APS (34%), infections (13%) and cancer (13%). SLE-related
deaths occured due to active disease (pulmonary or cerebral hemorrhage) in a third of patients and due to end stage organ failure (renal or
cardiac) in the rest. Deaths due to infections and active disease prevailed in the first five years of disease, while demise by catastrophic
APS or cancer occured predominantly afterwards. The global mortality was 13%, and overall survival rates at 5- and 10-years were 93%
and 88%, respectively. The survival curves of patients with and without lupus nephritis diverged in the first 20 years of disease, showing
greater mortality in patients with renal involvement; however, lupus
nephritis was not a major determinant for survival upon univariate
analysis. The multivariate analysis of risk factors identified a predictive
model consisting in a cumulative damage score 3 (p0.003), neuropsychiatric involvement (p0.05), associated antiphospholipid syndrome (p0.04) and advanced age (p0.008).
Conclusion: Long-term prognosis remains poor in patients with severe
disease and associated antiphospholipid syndrome, highlighting the
need to reduce damage accrual and improve the management of catastrophic APS in SLE patients.
References
1 Cervera R, et al. Medicine 2003;82:299-308.
A040
THE CLINICAL FEATURES OF SYSTEMIC LUPUS
ERYTHEMATOSUS PATIENTS FOLLOWED UP AT A SINGLE
CENTER IN THRACE REGION OF TURKEY
Pamuk O.N., Donmez S., Calayr G.B. and Mengus C.
Trakya University Medical Faculty, Department of Internal Medicine,
Division of Rheumatology, Edirne, Turkey
Introduction/Aim: We evaluated the clinical features, treatment modalities, treatment responses and prognosis of systemic lupus erythematosus (SLE) patients diagnosed at our center in Thrace region of
Turkey. We also estimated prevalence and incidence of SLE in our
region.
Patients and Methods: We retrospectively evaluated 279 patients (260F,
19M, mean age: 38.711.6 years) diagnosed with SLE between 20032013. Clinical features, treatments and responses to various treatment
modalities were recorded. Our hospital has been the only tertiary referral center for rheumatological diseases for a mixed rural and urban
population of 616000 people for >16 years (316000M, 300000F).
Results: The mean annual incidence of SLE was 4.5/100000
(females,8.7/100000; males,0.6/100000). The overall prevalence of
SLE was 45.3/100000 (females,86.7/100000; males,6.1/100000). Major
organ involvement was present in following percentages: neurologic
involvement, 20.1%; renal involvement, 28.2%; autoimmune hemolytic anemia, 9.6%; and trombocytopenia, 14.7%. Thirteeen SLE
patients (10 females, 3 males) died at a median follow-up of 49
months. The 5-year survival was 95%, and the 10-year survival was
92%. According to Kaplan-Meier survival analysis, poor prognostic
factors were being male (5-year: 77% vs. 95%, p0.015); having
pleural involvement (5-year: 95.4% vs. 87%, p0.011); having renal
involvement (5-year: 88.4% vs. 98.5%, p0.014); usage of cyclophosphamide (5-year: 87.3% vs. 96.6%, p0.004); and an initially high
SLEDAI score (>6) (5-year: 89% vs 97.8%, p0.005). According to
Cox regression analysis, pleural involvement (OR: 6.25, p0.018),
hemolytic anemia (OR: 4.1, p0.05), renal involvement (OR: 4.8,
p0.045), and low C3 level at the time of initial diagnosis (OR: 5.1,
p0.038) were independent poor prognostic factors which influenced
survival.
Conclusions: Our study demonstrated that the annual incidence and
prevalence of SLE in Thrace region of Turkey were quite similar to
western data. In our series, majority of patients were females. Survival
was similar to data from western countries. Renal involvement, pleural
involvement, initially active disease and autoimmune hemolytic anemia
were poor prognostic factors.
A041
THE CRETAN LUPUS COHORT LETO: PREVALENCE,
CLINICAL FEATURES AND ENVIRONMENTAL FACTORS IN
A GENETICALLY HOMOGENOUS, MIXED URBAN AND
RURAL SOUTH EUROPEAN POPULATION
Gergianaki I.1,2, Fanouriakis A.1, Repa A.1, Kallitsakis I.1,
Kabouraki E.1, Spyrou G.1, Tzanakakis M.1, Melissourgaki M.1,
Mamoulaki M.3, Katzakis P.3, Chatzi L.4, Sidiropoulos P.1,2,
Boumpas D.T.2,5 and Bertsias G.1,2
1
Heraklion, Greece 2Institute of Molecular Biology-Biotechnology,
FORTH, Greece 3Rheumatologist 4Department of Social Medicine,
University of Crete, Greece 5University of Athens, Athens, Greece
Introduction: Crete is the third largest and southernmost island in the
Mediterranean with a relatively stable, genetically homogeneous population of 0.6M inhabitants, thus offering the opportunity to study the
prevalence, etiopathogenesis and natural history of complex diseases
such as systemic lupus erythematosus (SLE). In Crete, 53% of the
Lupus
465
inhabitants reside in rural, 8% in suburban (10,000-15,000 dwellers)
and 39% in urban areas (>10,000 dwellers).
Aim: To establish a Cretan cohort of SLE patients and register their
demographic and clinical characteristics. To monitor environmental
exposures in association with disease outcomes.
Patients and Methods: The Department of Rheumatology, University
of Crete, serves as the referral center for patients with rheumatic diseases in Crete and has an extensive network that captures primary and
secondary care including private rheumatologists. All hospital records
were reviewed and all in- and outpatients diagnosed with SLE (4
ACR criteria) were prospectively evaluated. Rheumatologists working
in private practice were also contacted to recruit additional patients.
Socio-demographic, past medical history, and clinical characteristics
(including disease activity, flares, damage, and quality of life scores)
are electronically registered using structured forms.
Results: A total of 635 SLE patients aged 15 years who reside permanently on Crete were identified, corresponding to a disease prevalence of 123 per 100,000. The average age at the time of diagnosis is 41
(15) years (range 9-73) and female:male ratio 6.2:1. Eighty eight
(14%) patients have biopsy-proven lupus nephritis and 46 patients
(7%) have neuropsychiatric lupus. Urbanization, sunlight exposure,
tobacco and alcohol use, adherence to Mediterranean diet, as well as
major stressful events are monitored using validated questionnaires
and their effects on disease outcomes, such as flares and severe manifestations, is prospectively examined.
Conclusion: Longitudinal studies with genetically homogenous, mixed
urban and rural population in a setting that combines primary, secondary and tertiary care, are instrumental in the description of complex disease such as SLE, and in determining socio-demographic,
environmental and other factors that affect its natural history.
A042
TREATMENT AND OUTCOME OF JUVENILE SYSTEMIC
LUPUS ERYTHEMATOSUS IN PEDIATRIC UNITE, INSTITUTE
OF RHEUMATOLOGY BELGRADE, SERBIA
Stojanovic R.1,2, Stanimirovic B.3, Susic G2 and Novakovic D.2
1
University of Belgrade, School of Medicine 2Institute of Rheumatology,
Belgrade, Serbia 3Clinical Center Banja Luka, Banja Luka, Bosnia and
Herzegovina
Introduction: Juvenile systemic lupus erythematosus (jSLE) is autoimmune disease with 15-20% onset in childhood and adolescent age.
Aim: To describe experience in the treatment and outcome of disease in
children and adolescents with jSLE.
Patients and Methods: The medical records of patients with jSLE treated in the period 2001-2011 were reviewed. The diagnosis was established using ACR updated criteria (1997). Outcome was classified as:
remission -no clinical signs of disease and with normal lab parameters
during six months; satisfactory control of disease -one unlimited sign of
disease; active disease -two or more signs of disease, and death.
Results: Thirty seven patients (36 f, 1m) with jSLE were reviewed. The
mean age at disease onset was 15.192.7 years (range 7-19 yrs.) Period
from first symptoms to established diagnosis was 3.2 months. The
duration of jSLE was 5.196.5 yrs (1 month-30 yrs). The most
common features were mucocutaneus (96.9%), musculoskeletal
(93.9%) and hematological (90.9%). Lupus nephritis occurred in
45.5% of children. CNS manifestations in 51.2%. ANA was positive
in 97.3%, Anti dsDNA in 81.1%, Anti Sm in 40 % and APA were
positive in 37.3% of patients. Corticosteroid treatment was given in all
patients as prednisone (100%) or methylprednisolone pulses (58,8%).
Drugs used were: antimalarics in 97.3% of patients, azathiophrine
(48.6%), micophenolat-mofetil (21.6%) and cyclosporine (3,8%).
Outcome of jSLE was: remission in 1 patient (3%), satisfactory control
in 19 (57.5%), and active disease in 14 (42.4%) pts. Two patients died
from secondary antiphospholipide syndrome after 10 and 14 yrs, and

one patient died from multiple brain abscesses during sepsis, 7 months
after diagnosis of jSLE.
Conclusion: Satisfactory controlled disease was in half of the patients,
active disease in 38% of patients and three pts died. It is necessary to
improve diagnostic methods, follow up of out-patients and especially
the treatment with new therapeutic approach.
A043
TRENDS OF MORTALITY ASSOCIATED TO SYSTEMIC
LUPUS ERYTHEMATOSUS IN FRANCE: A MULTIPLE CAUSEOF-DEATH ANALYSIS
Chiche L.1, Thomas G.1, Jougla E.2 and Harle J.R.1
1
La Conception hospital, department of internal medicine, Aix-Marseille
University, Marseilles, France 2CepiDc, inserm, Paris, France
Introduction: The overall mortality rate of Systemic Lupus
Erythematosus (SLE) has improved significantly over the past 50
years but is still high as compared with the general population.
Aim: To analyze the mortality profile related to SLE in France.
Patients and Methods: For the 2000-2009 period, data collected in the
French Epidemiological Center for the Medical Causes of Death
(CepiDc) database and corresponding to death certificates of adults
(n1593) on which SLE was listed as an underlying (n637) or nonunderlying cause (n956) of death were analyzed using multiple causeof-death analysis. Gender, age, sex-ratio, standardized mortality rates
as well as the respective weight and frequency of the various causes of
death were assessed, both at national and regional level. The observed/
expected death ratio (O/E ratio) was calculated for the main causes of
death.
Results: Mean age at death was 63.5 17.3 years. Sex-ratio was 3.5.
The mean standardized mortality rate was 3.2 per 106 people. For SLE
as an underlying cause, the main non-underlying causes of death were
cardiovascular diseases (49.5%), infectious diseases (24.5%) and renal
failure (23.2%). For SLE as a non-underlying cause of death, the most
common underlying causes of death were cardiovascular diseases
(35.7%), neoplasms (13.9%) and infectious diseases (10.3%). The
overall death O/E ratio was > 1 for infectious and cardiovascular diseases and renal failure (especially for people < 40 years of age for the 2
last causes), but was <1 for neoplams. In overseas departments, the
standardized mortality rate was higher (10.8 / 106 people) and the
mean age of death was earlier.
Conclusion: Cardiovascular diseases are the most important cause of
death associated to SLE in France with a significant excess of mortality
compared to general population. It is therefore essential to improve
therapeutic and preventive interventions in this population and
improve survival in SLE.
A044
VERY LONG-TERM RENAL OUTCOME OF LUPUS
NEPHRITIS: A SINGLE CENTRE EXPERIENCE
Tani C.1, Carli L.1, Vagnani S.1, Querci F.1, Tavoni A.1, dAscanio A.1,
Neri R.1, Bombardieri S.1 and Mosca M.1
1
Rheumatology Unit, Department of Clinical and Experimental
Medicine, University of Pisa, Italy
Introduction: Lupus nephritis (LN) is a common manifestation of
Systemic Lupus Erythematosus (SLE), affecting up to 60% of patients;
aggressive immunosuppressive therapy has considerably improved the
patients survival but long-term renal outcome is still an open issue. In
this study we aimed at describing the very long-term renal outcome of
a monocentric cohort of SLE patients.
Lupus
466
Methods: In this retrospective observational study, SLE patients with
evidence of LN were evaluated; only patients followed for at least 10
years at our centre were included in the analysis.
Results: Among the 250 patients with LN of our cohort, 113 had at
least 10 years of fu (median since renal disease onset: 16.56 years, min
10-max 36). All Caucasian, the median age at renal disease onset was
30.711 years and the mean time between SLE diagnosis and LN
resulted 4.32 years. An histological LN class diagnosis was available
in 105 patients (II:7, III 10, IV: 84, V: 3). At the time of the biopsy, all
patients were positive for ANA, 78 (69%) for anti-dsDNA and 50
(44%) for anti- phospholipids. 81% of patients received
Cyclophosphamide, 60(53%) Azatioprine, 38 (33%) Cyclosporine, 26
(23%) Mycophenolate Mophetile, 19 (17%) IvIg; 13 (11%) were also
treated with plasma exchange while only 2 (1.7%) received Rituximab.
The cumulative GC dosage was 31.7 g19 (min 5 max 140 g). At our
last observation, the median age of the cohort was 4611 years (range
23-82); the mean creatinine value resulted 1.622.1 (min 0.4- max 11)
and the mean 24 hours proteinuria was 0.4g0.7 (min0-max 4) being 3
patients with nephrotic range proteinuria. Cumulatively, 39 patients
(34.5%) reached a poor renal outcome: 24 (21,2%) had a chronic renal
failure, 10 (8,8%) had an end stage renal disease and 5 (4,4%) had been
transplanted.
Discussion: In this retrospective cohort, despite treatment, more than
30% of patients reached a poor outcome after a mean of 16 years since
LN onset. Despite obvious differences in therapies and management
over the years, our data might offer a real-life representation of longstanding LN and of unmet needs on the treatment of this severe SLE
manifestation.
Diagnostic, classification and outcome criteria

A045
A CASE OF FEMALE PATIENT WITH PSORIATIC FORM
SUBCUTANEOUS LUPUS ERYTHEMATOSUS
Filipowska-Gronska A., Werynska-Kalemba M., Zawadzinska K.,
Filipowska B. and Jarzab J.
Clinical Department of Internal Medicine, Dermatology and
Allergology, Zabrze, Poland
Introduction: Subacute cutaneous lupus erythematosus (SCLE) is a
clinically distinct subset of cases of lupus erythematosus that is most
often present in white women aged 20 to 50. Characteristically the
lesions appear in sun-exposed areas such as the neckline or the forearms, but not the face.
Patiens and methods: We report a case of a 57-year-old female patient
suffering from subacute cutaneous systemic lupus erythematosus with
a one year history. Skin lesions were localized on the limbs, trunk,
scalp and vulva. Skin changes were characterized by erythema and
infiltration. There were covered by psoriasiform plaques.
Results: Histopathological examination taken from skin lesions
revealed perivascular lymphocytic infiltrates with intercellular edema,
thickening of the keratin and parakeratin. Indirect immunofluorescence examination revealed antinuclear antibodies (titer 1:640),
which fluorescence with HEP-2 cells was granular. Direct immunofluorescence examination revealed antibodies IgG in the epidermis.
The patient was treated by Encorton 30mg for eight month. Local
and general treatment had improved clinical status of the patients
skin. She is staying under clinical observation.
Conclusion: Based on the analyzed case we would like to present psoriatic form of SCLE, which clinically resembles psoriasis. Therefore, it
should be taken into account in the differentiation of these two skin
diseases.
A046
APPLICATION OF THE SYSTEMIC LUPUS INTERNATIONAL
COLLABORATING CLINICS CLASSIFICATION (SLICC)
CRTIERIA TO JUVENILE-ONSET SYSTEMIC LUPUS
ERYHTEMTAOSUS NEPHRITIS COHORT
Morgan TA.1,2, Lloyd O.1, Heaf E.1, Smith E.1,2, Beresford M.W.1,2 and
on behalf of the UK JSLE Study Group
1
Paediatric Rheumatology Department, Alder Hey Childrens Hospital,
Liverpool, UK 2Institute of Translational Medicine (Child Health),
University of Liverpool, UK
Introduction: Juvenile-onset SLE (JSLE) is reported to feature more frequent renal involvement than adult-onset SLE. The UK JSLE Cohort
Study, a large national inception cohort, enrols patients 18 years old
with 4 American College of Rheumatology (ACR) criteria and those
with probable evolving JSLE (<3 ACR criteria). In 2012 the SLICC
group proposed an alternative classification for SLE.(1) In these criteria,
biopsy-confirmed nephritis compatible with SLE in the presence of
ANAs or anti-dsDNA antibodies is sufficient for diagnosing SLE.
Aim:To identify amongst JSLE patients with biopsy-proven lupus
nephritis (LN) those meeting SLICC classification criteria but not
meeting ACR criteria for SLE.
Patients and Methods: Data was available for 353 patients at diagnosis
and latest follow up (median 3.2 years). 279 patients fulfilled 4ACR
criteria and 74 had 3 ACR criteria at time of diagnosis.
Results: 83/353 patients (24%) had a renal biopsy performed and 72/
353 (20%) had biopsy-proven LN. 10/72 (14%) patients with features
of LN on biopsy had <4ACR criteria but were ANA and/or dsDNA
positive, thus fulfilling the SLICC criteria in advance of meeting
4ACR criteria. Four patients still do not meet the ACR criteria at
latest follow up. Compared to those without biopsy-proven LN, neuropsychiatric lupus using both ACR and SLICC criteria, as well as the
presence of low C3 concentrations, were significantly more frequent in
patients with biopsy-proven LN at first presentation (see Table 1).
Conclusions: Application of SLICC classification criteria to patients in
whom renal biopsies were undertaken increased the chance of a diagnosis compared to using ACR criteria alone. SLICC criteria may
improve sensitivity for diagnosis of JSLE, enabling earlier diagnosis
within a paediatric population. Those with biopsy-proven LN are more
likely to have severe disease (e.g. neurological manifestations) and
early diagnosis is therefore important.
References
1 Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR,
et al. Derivation and validation of the Systemic Lupus International
Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis and rheumatism 2012; 64(8267786.
Table 1. Clinical characteristics observed in JSLE patients with biopsy
proven nephritis
Biopsy
JSLE without biopsy
confirmed LN confirmed LN
72
281
12.8
12.2
Number Patients
Mean Age at diagnosis
(Years)
Female: Male Ratio
5.8: 1
Neurological Involvement
19%
(ACR Definition)y
(14/72)
Neurological Involvement
25%
(SLICC Criteria Definition)z (17/68)
Low baseline C3
77%
(41/53)
y
5.8: 1
8%
(23/281)
12%
(31/266)
43%
(93/217)
p 0.003
p 0.004
p 0.006
Recorded as of latest visit

Recorded as of latest visit: SLICC Criteria for Neurologic Involvement(1)
(seizures, psychosis, mononeuritis multiplex, myelitis, peripheral or cranial
neuropathy or acute confusional state)
z
Lupus
467
A047
FACTORS ASSOCIATED WITH TIME TO DIAGNOSIS IN
SYSTEMIC LUPUS ERYTHEMATOSUS IN MOLUSTUDY
Mazur-Nicorici L.1, Revenco N.1, Ch. Baerwald2, Vetrila S.1,
Sadovici V.1, Cebanu M.1 and Mazur M.1
1
SUMPh Nicolae Testemitanu, Republic of Moldova 2Leipzig
University, Germany
Introduction: During the past decades it was established an increase of
the survival rate from a 5 year in the 1950s to a 10 years survival rate
of 90% in 1990s [1]. This improvement was related to a better undesrtanding in the immunopathogenesis of SLE, early detection of cases,
use of corticosteroids and immunosupressive drugs [2].
Aim: To determining the time from onset of symptoms (OS) until the
diagnosis of SLE patients in Republic of Moldova.
Patients and methods: The study cohort included patients from
Moldova Lupus Study (MoLuStudy) diagnosed with SLE fulfilling
at least 4 of the 1997, ACR revised criteria. The SLE disease activity
was determinated using the SLEDAI and SLAM scores.
Results: We examinated 108 patients, 99 female (91,7%), mean age SD
39, 6 12,1 years (well-described signs or symptoms that were compatible with the disease- cutaneus manifestation, arthralgia, psihoneurological involvement, fever and immunological or hematological
abnormalities), mean disease duration was SD 108 12,9 months.
The disease activity by SLEDAI was 12,2 10,0 and SLAM - points.
The mean time duration from the (OS) to first medical contact (FMC)
was 2,65 3,1, the mean time from the FMC to diagnosis and start of
treatment of SLE was 3,47 8,7 months. We established a significant
correlation between the onset of symptoms until the first medical contact with disease activity (r 0,392) and was appreciated a good correlation between speedy addressing patient with intermediate and high
level of education (r 0,432) and (r0,451), respectively.
Conclusion: Increase the time from first symptoms to initiation of treatment involves high activity and significant correlation with low level of
education.
References
1 Kasitanon N, et al. Causes of Death and Prognostic Factors in Thai
Patients with SLE. Asian Pacific Journal of Allery and Immunology
2002; 20: 8591.
2 Hedrich CM, et al. Early onset systemic lupus erythematosus: differential diagnoses, clinical presentation, and treatment options.
Clin Rheumatol 2011 Feb; 30(227583.
A048
FLARE RATES IN SYSTEMIC LUPUS ERYTHEMATOSUS: A
LONGITUDINAL COHORT COMPARING CLINICAL
FEATURES, DEMOGRAPHICS AND USE OF
HYDROXYCHLOROQUINE IN PATIENTS WITH AND
WITHOUT FLARES
Makaronidis J., McElhone K. and Teh L.S.
East Lancashire Hospitals NHS Trust, Blackburn, United Kingdom
Introduction: SLE is a complex disease, characterized by variable presentations and a relapsing-remitting nature. It has been suggested that
younger patients, those with lupus nephritis and on immunosuppressive treatment are at risk of flares whilst hydroxychloroquine reduces
flare rates.
Aim: This observational cohort study compared clinical features,
demographics and use of hydroxychloroquine in patients with and
without flares, aiming to identify predictors of flares.
Patients and Methods: A cohort of patients with SLE under the care of
one Rheumatology department was observed for 18 months. Patients
with new A or B flares using the BILAG-2004 index were followed up
monthly for 9 months. At baseline, demographic data, current treatment and BILAG-2004 scores were recorded. At each monthly visit,
BILAG-2004 scores and treatment changes were collected. The
patients were separated into two groups (flare or non-flare).
Descriptive statistics and student t-tests were used to compare the
groups.
Results: There were 78 patients in the cohort. 18 developed a new A or
B BILAG-2004 flare in 18 months, giving a flare rate of 15.4%. There
were no differences between the two groups with regards to gender or
duration of SLE. Ethnicity in the flare and non-flare patients was:
White/Caucasian
(66.6%,71.2%),
Asian/Pakistani/Indian
(33.3%,24.5%) and Black African/Carribean (0%,3.4%). The patients
who flared were younger (mean SD, 45.513.5, 51.2 14.8) and
younger at diagnosis (31.213.8, 3713.9). 94.7% of the patients
who flared had at least one re-flare. There were 44 baseline and 65
re-flare episodes. The frequency of the systems affected at the initial
and subsequent flares were: cardiorespiratory (20.5%,23.1%), mucocutaneous (22.7%,21.5%), musculoskeletal (20.5%,17%), neuropsychiatric (11.4%,9.2%), constitutional (11.4%,7.7%), gastroenterology
(9%,6.2%), renal (4.5%,12.3%) and haematology (0%,3%). 50% of
flare patients were not on hydroxychloroquine compared to 24% of
non-flare patients (P0.039).
Conclusions: Younger patients with a younger age of onset of SLE
tended to flare. A larger proportion of patients who did not flare
were on hydroxychloroquine.
References
1 Gordon C., et al. Definition and treatment of lupus flares measured by the BILAG index.. Rheumatol 2003; 42.11: 13721379.
2 Ines, Lu s, et al. Identification of clinical predictors of flare in
systemic lupus erythematosus patients: a 24-month prospective
cohort study.. Rheumatol 2014; 53.1: 8589.
3 Yee, Chee-Seng, et al. Numerical scoring for the BILAG-2004
index.. Rheumatol 2010; 49.9: 16651669.
4 Bertsias G., et al. EULAR recommendations for the management
of systemic lupus erythematosus. Report of a Task Force of the
EULAR Standing Committee for International Clinical Studies
Including Therapeutics.. Ann Rheum Dis 2008; 67.2: 195205.
A049 WITHDRAWN
A050
IS THE QUALITY OF LIFE INFLUENCED BY THE DISEASE
ACTIVITY IN PATIENTS WITH SYSTEMIC LUPUS
ERYTHEMATOSUS?
Sadovici V.1, Ch. Baerwald2, Cebanu M.1, Pasali M.1, MazurNicorici L.1 and Mazur M.1
1
SUMPh Nicolae Testemitanu, Moldova 2Leipzig University, Germany
Introduction: Patients with systemic lupus erythematosus (SLE)
improved their 10-year survival during the last 40 years [1]; therefore,
other outcome measurements, as the Quality of Life (QoL), gained
importance [2]. In the literature, the data on the relationship between
the QoL and the dis ease activity are contradictory [2, 3].
Aim: To assess the QoL and to establish its correlation with the disease
activity and global assessments in lupus patients
Patients and methods: Cross-sectional study including patients fulfilling
the SLICC 2012 SLE criteria. The disease activity was appreciated by
SLEDAI and SLAM; general assessments by PGA and MGDA. All
patients completed the Sf-8 questionnaire, estimating physical and
mental component summaries (PCS and MCS).
Results: We examined 30 patients, 100% females, mean age SD
40,411,9 years, mean disease duration SD 5,06,6 years. The
Lupus
468
disease activity by SLEDAI and SLAM was 7,710 and 7,87,4; PGA
and MGDA represented 42,631,0 and 39,326,8, respectively. The
PCS and MCS were 43,29,6 and 46,913,4, the QoL being low by
both components.
We established a close significant negative correlation between PCS
and disease activity, as shown in the table. The MCS did not correlate
with disease activity scores.
Conclusion: The Physical Component Status of the QoL has a high
indirect correlation with the disease activity and global assessments
in patients with Systemic Lupus Erythematosus.
Table 1.
PCS
MCS
Correlation Coefficient
p
Correlation Coefficient
p
SLEDAI
SLAM
PGA
MGDA
-0,787
0,0024
-0,182
0,5705
-0,830
0,0008
-0,130
0,6882
-0,823
0,0034
-0,357
0,3116
-0,837
0,0025
-0,112
0,7586
References
1 Merola JF. P937: Changes in Ten Year Survival Among SLE
Patients At an Academic Center in North America (1970-2011).
Presented at: ACR 2012 Annual Meeting; Nov. 10-14, Washington.
2 Kiani A.N., Petri M., Quality-of-Life Measurements Versus Disease
Activity in Systemic Lupus Erythematosus, Curr Rheumatol Rep
2010, 12:250.
3 Khanna S. and co. The relationshio between disease activity and quality of life in systemic lupus erythematosus, Rheumatol 2004, 43:1536.
A051 COPYRIGHT PROTECTED. NOT FOR PUBLICATION
A052
OUTCOME OF ADULTS WITH CHILDHOOD ONSET

SYSTEMIC LUPUS ERYTHEMATOSUS IN SAUDI ARABIA
Al Hamzi H.1, Alhaymouni B.1, Al Shaikh A.1 and Al-Mayouf S.M.2
Adult Rheumatology1, Pediatric Rheumatology2 King Faisal Specialist
Hospital and Research Center, Riyadh
Objective:To describe the social, educational, employment and long
term clinical outcomes of adults with childhood onset systemic lupus
erythematosus (SLE) in Saudi cohort.
Methods: All adult patients with childhood onset SLE treated between
1990 and 2013 at King Faisal Specialist Hospital and Research Centre
(KFSH-RC), Riyadh and continued to be followed at KFSH-RC are
included. The long-term outcome measured by SLE Disease Activity
and Damage Indices at last follow up visit and death related to SLE
were determined. Social, educational and employment history and
quality of life were obtained via personal or phone interviews.
Results: 48 patients (45 female) were included. The mean age was 23.6
4 years while the mean disease duration was 15 4 years. At last
follow up visit, 24 (50%) patients were found to have active disease
(SLEDAI > 4), with mean of damage index of 2 (0-7). Forty patients
(83%) had renal involvement, 7 (15%) of them progressed end stage
renal disease, 4 patients underwent renal transplant, 2 failed the transplant and currently on hemodialysis. Central nervous involvement was
found in 16 patients in the form of seizure disorder (6 patients), chorea
(3 patients) and cerebrovascular accident (3 patients). There were 3
deaths related to SLE (6.25%), mainly due to infection.
Forty three patients had completed secondary high school, 21 of them

started college. Six patients had got work. Eight patients got married
and 5 of them have children
Conclusions: Our cohort indicates that the outcome of adult patients
with childhood onset SLE was satisfactory and comparable to previous
reports.
A053
RELATIONSHIPS BETWEEN MINOR NEUROPSYCHIATRIC
EVENTS AND SYSTEMIC LUPUS ERYTHEMATOSUS:
PERFORMANCE OF AN ATTRIBUTION MODEL
Bortoluzzi A.1, Scire` CA.2, Padovan M.1 and Govoni M.1
1
Section of Haematology and Rheumatology, University of Ferrara and
Azienda Ospedaliero-Universitaria SantAnna di Cona, Ferrara
2
Epidemiology Unit, Italian Society of Rheumatology, Milan, Italy
Introduction: Neuropsychiatric (NP) involvement in Systemic Lupus
Erythematosus (SLE) presents with a variety of neurologic and psychiatric syndromes. Their relationship with the underlying disease
could be difficult to assess especially for mild, diffuse and nonspecific
NP syndromes such as, headache, mild depression and anxiety.
Aim: To test the performance of an attribution model applied to mild
NP events in a large mono centric cohort of SLE patients.
Patients and Methods: NP events were defined according to the 1999
ACR case definitions and re-assessed using a previously developed and
validated attribution model, including a weighted score of 4 different
items: onset time of the NP event; presence of non-SLE confounding
factors (i.e. associations as suggested by the 1999 ACR criteria); presence of specific NP events according to Aniala; presence of favouring
factors (general and disease specific). Expert opinion was set as reference standard of the attribution of NP event to SLE. The relationship
between the attribution model and the reference diagnosis was evaluated by logistic models, and results presented as odds ratio (OR) and
95% confidence intervals (CI), and standardised coefficients.
Performance was evaluated by the Area Under the ROC Curve (AUC).
Results: A total of 126 patients with a diagnosis of SLE according to
the revised ACR classification criteria with one NP minor event (86
headache, 31 mild depression, 9 anxiety) were included: M/F 5/121
females, with a median age at first NP event of 38 years. The overall
performance of the model was good (AUC 0.754 (0.675-0.832). The
most important items for correct classification was the confounding
factor sub-score OR (95%CI)/stand. coeff. 15.86 (3.59-70.03)/1.27,
with a lower contribution for onset time 2.18 (1.22-3.92)/0.61, and
additional factors 2.71 (1.51-4.85)/0.75.
Conclusion: Despite experts opinion remains the gold standard, using
an assignment algorithm may improve the correct attribution of minor
NP events to SLE.
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469
Clinical features, diagnosis and co-morbidities

A054
A CASE OF PATIENT WITH PSORIASIS- LIKE SUBACUTE
CUTANEOUS LUPUS ERYTHEMATOSUS
Krajewska A., Werynska-Kalemba M., Zawadzinska K., Pagacz J. and
Jarzab J.
Chair and Clinical Department of Internal Diseases, Dermatology and
Alergology in Zabrze, Medical University of Silesia, Poland
Introduction: Subacute cutaneous lupus erythematosus (SCLE) is a
clinically distinct subset of benign cases of lupus erythematosus without organs lesions. The most often is presented in white women aged
15 to 40, consisting of skin lesions that are scaly and evolve as polycyclic annular lesions or psoriasiform plaques. In the most of cases 4
ARA criteria are implemented. Generally skin lesions disappear spontaneously during 6 month period. Tansformation to lupus erythrematosus is possible. This process is rare and it is taking many years from
the first diagnosis.
Patients and methods: 63-years female patient hospitalizated repeatedly
in Chair and Clinical Department of Internal Diseases, Dermatology
and Alergology in Zabrze beetwen 2011 and 2013. In the beging of
observation only psoriasis like skin lesion were observed. Then typical
butterfly face rush, sensivity to sunlight and accompanying arthralgia have joined. During the observation the diabetes, cholelithiasis,
renal cyst were diagnosed. The patient have had numerous blood analysis, including lues tests, chest X-rey, abdominal ultrasonography, two
histopathology examination of skin section, direct immunofluorescence and allergy tests. She also has cardiac, laryngological, hematological and rheumatological consultation.
The patient is steal staying under clinical observation.
Results: During hospitalization in 2011 in the first histopathology (HP)
examination diagnosed ezgema with accompanying positive ANA
antybodies (1:640). Examination of ANA3 profile has shown presence
of SSA, SSB and Ro-52 autoantybiodies. The patient has been hospitalizated again in 2012 the second histopathology and direct
immunofluorescence (DIF) were made. The HP test stated psoriasis
lesions, DIF common autoantybodies. Coexistence of leukopenia
was observed.
In treatment topical steroides, exfoliative medicaments, antybiotics,
methotrexat and acitretin were used with average improvement.
Conclusions: Based on the analysis case we would like to present clinical difficulties that can occur during diagnosing psoriasis-like SCLE.
A055
A PROSPECTIVE STUDY IN PREMENOPAUSAL WOMEN
WITH SYSTEMIC LUPUS ERYTHEMATOSUS
SUPPLEMENTED WITH TWO DIFFERENT REGIMES OF
VITAMIN D: EFFICACY AND SAFETY AT 12 MONTHS OF
FOLLOW-UP
DallAra F., Andreoli L., Piantoni S., Piva N. and Tincani A.
Spedali Civili and University of Brescia, Rheumatology and Clinical
Immunology,Brescia, Italy
Introduction: Systemic Lupus Erythematosus (SLE) patients (pts) are
at risk for low vitamin D(VitD) levels because of lack of sun exposure.
Few prospective studies are available on the effects of VitD
supplementation.
Aim: To evaluate at 12months of follow-up (T12) efficacy, safety and
the effects on SLE disease activity of an oral Cholecalcipherol supplementation given with 2different regimens.
Patients and methods: 34SLE women were enrolled. A group of 18pts
(group S) were given standard regimen of supplementation
(Cholecalcipherol 25.000UIonce/month).The other 16pts (group I)
were given an intensive regimen (Cholecalcipherol 300.000UI
bolus, then 50.000UIonce/month).The circulating levels of 25OHVitD were dosed every 3months with a chemiluminescence
assay(DiaSorin S.p.A.,Italy).
Results: At baseline(T0) there was no significant difference in VitD
levels in the 2groups. After 3,6,9 and 12 months group I showed
significantly higher VitD levels (median at T12:32.0vs24.8 p0,04). No
significant differences upon season of enrollment. At T0 there was no
difference in the proportion of sufficient pts (>30 ng/ml) between
groups (S:50%, I:56%), while at T12 sufficient pts were 28% in S
and 75% in I (p0.02). No significant variations in the levels of calcium, phosphorus and PTH.There were 3 cases of transitory mild
hypercalciuria (2 in I,1 in S).The pts had clinically quiescent disease
(median SLEDAI 2 in S, 4 in I), but serologically active disease (positive anti-DNA and/or complement consumption in nearly50% of the
pts).No statistically significant variation in the titers of anti ds-DNA
and in the levels of C3,C4,CH50 was observed at T12 in both groups.
Conclusions: Intensive supplementation with VitD has a safe profile as
the standard but it is able to induce sufficient levels in a larger number
of pts.No particular effects on serological SLE parameters was noted,more data will come from the second year of the study.
References
1 Cutolo M, et al. Vitamin D endocrine system and the immune
response in rheumatic diseases. Vitam Horm 2011; 86: 32751.
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470
A056
A057
A REVIEW OF METABOLIC SYNDROME IN SYSTEMIC

LUPUS ERYTHEMATOSUS: A DANGEROUS OUTBREAK
Zen M.1, Gatto M.1, Palma L.1, Borella E.1, Bruce I.2 and Doria A.1
1
Division of Rheumatology, University of Padua, Italy 2Arthritis
Research UK Epidemiology Unit, The University of Manchester, United
Kingdom
ANALYSIS OF SPECTRAL DOMAIN OPTICAL COHERENCE

TOMOGRAPHY (SD-OCT) FINDINGS IN PATIENTS WITH
SYSTEMIC LUPUS ERYTHEMATOSUS ON
HYDROXYCHLOROQUINE THERAPY
Ugarte A.1, Artaraz J.2, Arteagabeitia A.2, Fonollosa A.2,
Lerchundi T.X.2, Pernas B.1 and Ruiz-Irastorza G.1
1
Autoimmune diseases research unit. Hospital Universitario Cruces.
UPV/EHU 2Ophtalmology Department. Hospital Universitario Cruces.
UPV/EHU
Aim: To investigate the prevalence of Metabolic syndrome (Mets) and

its components in patients with systemic lupus erythematosus (SLE).
Materials and methods: We conducted a systematic search using Ovid
MEDLINE, PubMed Central, and SciVerse Scopus looking for casecontrol, cross-sectional and cohort studies including SLE patients with
measures of MetS. Restriction to English written papers was applied.
Systemic lupus erythematosus and metabolic syndrome, or terms
linked to each of MetS components (obesity, body mass index
(BMI), waist circumference, type 2 diabetes, hyperglycemia,
insulin resistance, hypercholesterolemia, hypertriglyceridaemia,
HDL cholesterol, and hypertension) were used as keywords.
Three established definitions of MetS (WHO, National Cholesterol
Education Program, or International Diabetes Federation) were considered. Articles considering less than 3 components of MetS were
excluded.
Results: A total of 74 studies were included, from an initial search of
4,578. 4,317 entries were excluded on the basis of titles and abstracts;
54 revision articles were excluded after screening; 133 studies were
excluded because they did not report outcomes of interest.
A total of 21,344 patients were included. 46 studies (58.3%) considered
all the components of MetS. Central obesity (2,089/4,607 patients,
45.3%), hypertension (8,044 out of 20,330 patients, 39.5%), and low
HDL cholesterol (1,406/3,940 patients, 35.7%) were common manifestations of MetS, whereas hypertriglyceridaemia (1,194/4,130
patients, 28.9%), high BMI (2,938/11,366 patients, 25.8%), and
impaired fasting glycemia (612/3,722 patients, 16.4%) had a lower
frequency.
MetS prevalence was reported in 23 studies, ranging from 10.4% to
41.4%. 864 out of 4,098 patients (21.1%) met the diagnostic criteria for
MetS.
Among 14 case-control studies, 10 (71.4%) demonstrated a higher
prevalence of MetS in SLE patients compared to controls.
Conclusions: This review presents clear evidence for a high prevalence
of MetS in different cohorts of SLE patients. Hypertension, obesity,
and hypertriglyceridaemia were the most common components of
MetS.
Diagnostic procedures for MetS should be routinely carried out in SLE
patients.
Title and abstract screened n=4578
Potentially suitable n=261
Objective: Spectral domain Optical Coherence Tomography (SD-OCT)

is one of the recommended screening tests for hydroxichloroquine
(HCQ) related retinal toxicity. The aim of this study was to evaluate
changes in SD-OCT in patients with systemic lupus erythematosus
(SLE) taking HCQ and to investigate whether they are related with
the cumulative dose or the duration of treatment.
Methods: Cross-sectional study in a group of 156 consecutive patients
with SLE on HCQ therapy from the Lupus-Cruces cohort. Each
patient had a complete ophthalmologic examination and the following
measurements with SD-OCT (Cirrus, Carl Zeiss): Macular Cube
518x128; HD 5 line raster. Two retina specialists analysed qualitatively
the scans for abnormalities in the retinal pigment epithelium (RPE)
and the outer retina (normal, any focal thickening or atrophy). We also
recorded quantitative data: average macular thickness and distribution
in normative data (normal within 5-95% interval; thickened >95%;
thinned <5%); thickness in each quadrant of the ETDRS grid; ganglion cell layer thickness and distribution.
We then compared abnormalities in SD-OCT in relation to HCQ
cumulative dose, duration of treatment, previous intake of chloroquine
(CQ) and recognised risk factors for HCQ toxicity (>1000 g cumulative dose and 8 years of treatment).
Results: 89% of the patients were female and 95% white. 19% had
qualitative abnormalities of the RPE or outer retina in either eye.
3.29% had atrophy of RPE, outer retina or both. Regarding quantitative data, 12 patients (8%) had thinning of the average macular
thickness (<5% of normative data) in either eye. There was no statistically significant difference in the cumulative dose of HCQ between
patients with atrophy of RPE/outer retina (474 617.5 g) and those
without (507.6 361.9 g). The same was true for quantitative thinning
of average macular thickness. Likewise, there was no difference in the
frequency of atrophy between patients who had never taken CQ (3 out
of 119) and patients who had taken it (2 out of 27). No difference was
found in the rest of the parameters studied (HCQ> 1000g, 8 years of
treatment, absolute duration of treatment). There was no correlation
between the average macular thickness and the cumulative dose of
HCQ.
Conclusions: In this cohort of SLE patients, there was no relationship
between abnormalities in SD-OCT and the dosage of HCQ. The incidence of atrophy of RPE/outer retina was low.
Excluded as not suitable n= 4317
Included after full text review n=74

Reasons for exclusion:
Reviews n=54
Not reporting outcomes of interest n=133
Lupus
471
A058
CARDIAC FUNCTION AND ARTERIAL STIFFNESS IN
JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS
Vieira R.1,3, Mota C.2, Moura C.2,3 and Brito I.1,3
1
Pediatric Rheumatology Unit 2Pediatric Cardiology Department;
Hospital Sao Joao, Porto, Portugal 3Oporto Faculty of Medicine,
Portugal.
Introduction: Cardiovascular events are the most common cause of
death in systemic lupus erythematosus (SLE). Impaired systolic and
diastolic function and increased arterial stiffness have been recognized
as surrogate markers of early cardiovascular disease in SLE.
Aim: to assess left (LV) and right (RV) ventricular function and arterial
elastic properties in a population with juvenile-SLE.
Patients and Methods: Cross-sectional evaluation of a juvenile-SLE
patients sample: two-dimensional, M-mode, conventional Doppler
and tissue Doppler imaging (TDI) to evaluate systolic and diastolic
biventricular function; aortic pulse wave velocity with standard technic
(Pulse Trace PWV , Micro Medical) to assess arterial stiffness.
Results: 17 females were included, median age of 20 years and median
disease duration of 8 years. The majority of patients presented at least
one criteria of LV diastolic dysfunction. Mitral E/A ratio was normal
in 8 patients and showed restrictive pattern in 4. E/E septal ratio
showed increased left atrium pressure in 2 patients. E/Vp ratio was
abnormal in 3 cases, predicting high mean pulmonary capillary
wedge pressure. Reduced propagation velocity (Vp) of the mitral
valve was observed in 4 cases, implying impaired relaxation. LV systolic function was preserved in all cases. RV systolic function was
normal in all patients except for one, with AoR: TDI S velocity 9.3
cm/s, tricuspid annular plane systolic excursion (TAPSE) 14.8 mm. RV
diastolic function markers were altered in some patients: decreased
peak velocity of E wave in 4 patients, with increased A wave velocity
in 1 patient. E/E and E/A ratios were normal in all cases. Arterial wave
velocity was within normal range in all tested patients (n11).
Conclusion: Almost all patients had subtle abnormalities of diastolic
function, even in the presence of preserved systolic function. Wave
velocity was normal in all patients which may relate to relative short
disease duration, absence of major cardiovascular risk factors and
young age sample. Evaluation of larger samples is required to consolidate our conclusions.
A059
CLINICAL AND LABORATORY PREDICTORS OF DISTINCT
HISTOLOGICAL CLASSES OF LUPUS NEPHRITIS
Mavragani C.P.1,2, Fragoulis G.E.2, Tzioufas A.G.2 and
Moutsopoulos H.M.2
1
Department of Physiology, School of Medicine, University of Athens,
Athens 2Department of Pathophysiology, School of Medicine, University
of Athens, Athens, Greece
proteinuria (NRP) were independently associated with III/IV histological classes. Age>44 years, malar rash, absence of MSK complaints
or leucopenia, NRP, and 9 erythrocytes/hpf in urinalysis were associated with type V lupus nephritis. A risk score for the prediction of
specific histological classes was calculated for each patient, with OR
[95%CI] for the presence of 3 of the aforementioned risk factors of
4.86 [1.99-11.85] for type II, 9.30 [4.09-21.13] for types III/IV and
7.61[2.76-21] for type V, respectively.
Conclusions: The identification of independent factors associated with
specific types of lupus nephritis and a risk score for prediction can
provide guidance in selecting specific therapeutic modalities, particularly in cases where renal biopsy is contraindicated.
A060
CLLINICAL OBSERVATION IN LUPUS PATIENTS WITH AND
WITHOUHT ANTIPHOSPHOLIPID SYNDROME. TEN YEARS
OF FOLLOW-UP
Tarr T., Gyo00 ri N., Szanto A., Nagy N. and Zeher M.
Department of Clinical Immunology, University of Debrecen, Hungary
Introduction: Systemic lupus eyrthematosus can bge associated with
antiphospholipid syndrome. Years ago our study team investigated
the thrombotic risk factors and complications in 272 lupus patients
with and without antiphospholipid antibodies. At baseline, three
groups were created, an aPL- group with 107 aPL negative patients,
an aPL group with 81 aPL positive patients without clinical manifestations and a secondary antiphospholipid syndrome (APS) group
with 84 aPL patients who met the Sapporo criteria.
Aims: The objective of this study was to investigate of new thrombotic
events, SLE activity,.co-morbidities, and mortality in total of 272 lupus
patients for ten years of follow up.
Patients and methods: The above mentioned 272 patients with SLE
registerered in the Clicical Immunolology Department, University of
Debrecen have been followed up prospectively for ten years.
Results: A total of 28 out of the 272 patients were lost to follow up. A
total of 22 new thrombotic complicatons occurred, two in the aPL
negative group, three in the aPL group. New antiphospholipid antibodies appeared in these patients. 77.3 % of the new thrombotic complicatins reoccured in the APS group despite the adequat anticoagulant
and/or anti-platlet therapy. SLE activity was the most common in the
APL group but the difference was not significant. A total of 27 out of
84 APS (32 %), 14 out of 81 aPL positive and 10 out of 107 aPL
negative patients died during the follow up. The causes of death
were thrombotic events or complications in 40.7 % in patients with
APS.
Conclusions: Our data confirm recurring thrombotic events in lupus
patients with antiphospholipid syndrome. Antiphospholipid syndrome
seems to negatively influence the survival of the patients with systemic
lupus erythematosus.
Introduction: The type of histological class of lupus nephritis dictates

treatment approaches among lupus patients with renal involvement.
Risk stratification may facilitate therapeutic decisions, when renal
biopsy is contraindicated or poses high patient risk.
Aim: To develop risk scores predicting distinct classes of lupus nephritis by using clinical variables and simple laboratory measures.
Patients and Methods: 163 consecutive patients with biopsy-confirmed
lupus nephritis. A risk score was developed to estimate the risk for
developing distinct histological classes of lupus nephritis.
Results: Variables independently associated (p<0.10) with type II class
included age 44 years, no malar rash, negative anti-DNA and 5
urine leucocytes. The presence of musculoskeletal (MSK) manifestations, new-onset hypertension, positive anti-dsDNA, >5 urine leucocytes/hpf, creatinine levels>1.2mg/dl and absence of nephrotic range
Lupus
472
A061
COMPARISON OF CLINICAL PRESENTATION AND
IMMUNOLOGICAL PROFILE IN SLE PATIENTS WITH THE
DISEASE ONSET AFTER THE AGE OF 50 AND IN SLE
PATIENTS AGED OVER 50
onska D.2, Honczarenko K.3,
Ostanek L.1, Boborowska-Snarska D.1, Pl
Fischer K.1 and Brzosko M.1
1
Clinic of Rheumatology and Internal Diseases Pomeranian Medical
University 2Clinic of Cardiology PUM 3Clinic of Neurology PUM
Introduction: Systemic lupus erythematosus (SLE) most often occurs
between the age of 20 - 40 years. Patients sex, age, and the age at the
disease onset influence the disease course.
Aim: The aim of the study was to compare the clinical presentation and
immunological profile in patients with SLE onset after the age of 50
and in SLE patients aged over 50.
Subjects and methods: 183 SLE patients aged 17-79 were examined. The
patients undervent physical examination with echocardiography,
neurological examination, and additionally electrophysiological examination and imaging tests (MRI and SPECT). Apart from standard
tests, assays for antibodies specific for SLE and for antiphospholipid
syndrome were performed. SLE activity was assessed with SLEDAI
index.
Findings: SLE female-to-male ratio decreases with age. It was the
lowest (4:1) in patients with SLE diagnosed at the over age of 50
years. Anti-histone antibodies were more often identified in patients
under 50 years of age (p0.013). Anti- Sm antibodies were more often
identified in patients with late onset SLE (p0.043), but anti-cardiolipin antibodies and anti b2GPI were less often identified in patients
with late onset SLE than in patients with early onset SLE (p0.035).
Serositis and polyneuropathy were more frequent in older patients
(p<0,05), but anemia was far more frequent in patients with late
onset SLE (p0.006). Thrombosis was equally common in both
groups, and they were more frequent than in other patients
(p0.0210). Lesions detected by echocardiography and coronary
heart disease symptoms were equally frequent in both groups; they
were more frequent than in younger patients and in patients with
SLE diagnosed before the age of 50 years (p<0.05).
Conclusions: Despite numerous similarities related to age, there are
differences in clinical presentation and serological profile in SLE
older patients and in patients with late onset SLE.
A062
DEPRESSED MOOD AND ANXIETY ARE COMMON IN SLE,
AND VARY DURING FOLLOW-UP INDEPENDENTLY OF
DISEASE ACTIVITY
Bengtsson A.A.1, Gullstrand B.2, Lood C.2 and Jonsen A.1
1
Department of Clinical Sciences, Section of Rheumatology, Lund
University, Lund, Sweden 2Department of Laboratory Medicine, Section
of Microbiology, Immunology and Glycobiology, Lund University, Lund,
Sweden
Introduction: Mood disorders are common in SLE. Our hypothesis was
that a higher disease activity and activation of the type 1 interferon
system would be reflected in an increase in depressive symptoms and
anxiety, as well as in a decrease in serum serotonin concentrations.
Aim: To study anxiety and depression in SLE in a longitudinal setting and
to correlate symptoms with disease activity and type 1 interferon activity.
Patients and methods: Consecutive SLE-patients (n67) were included
in a longitudinal follow-up cohort with visits every 2 months for 2 years.
At every visit patients completed the Hospital Anxiety and Depression
scale (HAD) and disease activity was recorded using the SLE disease
activity index 2k (SLEDAI-2k). Serotonin concentration was determined in serum, together with Galectin 3 Binding Protein (G3BP) as a
marker of type 1 interferon system activation. Variables were dichotomized due to statistical considerations. For statistical analyses we used
Generalized Estimating Equation to handle correlated data.
Results: The number of visits included in the study was 677. Forty-nine
percent of the patients displayed a HAD anxiety score >8 on at least
one occasion during follow-up and the corresponding number for
HAD depression score was 42%. A large variation could be seen in
total HAD score with a mean difference per patient between the maximum and minimum scores during the follow-up time of 10.3 and a
mean standard deviation for the percent change per patient of 0.37.
HAD depression and anxiety scores were not associated with SLEDAI
scores, G3BP concentrations or serotonin levels.
Conclusions: Clinically significant anxiety and depression is common in
SLE during follow-up. Furthermore, anxiety and depression scores display a variation over time in SLE in the individual patient. Disease
activity, type 1 interferon activation and serotonin levels may be less
influential in determination of SLE-related mood disorder.
A063 WITHDRAWN
A064
INVESTIGATION OF CHRONIC ORGAN DAMAGE IN
PATIENTS WITH SYSTEMIC LUPUS. RESULTS OF A
HUNGARIAN IMMUNOLOGYICAL CENTRE
Gyo00 ri N.1, Siminszky Zs.1, Cserep E.2, Szanto A.1, Zeher M.1 and
Tarr T.1
1
Department of Clinical Immunology, University of Debrecen, Debrecen,
Hungary; 2Department of Psychiatry, University of Debrecen, Debrecen,
Hungary
Introduction: The long term survival of patients with systemic lupus
erythematosus has progressively improved wordwide. The prevention
of organ damage become one of the major aims in the management of
lupus patients.
Aim: The goal of our study was to investigate the chronic organ damages in patient with sytemic lupus registerered in the Clicical
Immunolology Department, University of Debrecen.
Patients and methods: The authors analyse retrospectively the results of
357 lupus patients with using the internationally accepted SLICC/ACR
damage index.
Results: We detected one or more organ damage score in 77,87 % of
our patients, the highest score was 8. Almost half of the patients
(46,50%) had one or two damage(s). The gender did not influence
the score of the damage index. The SDI has become significantly
higher after the first 10 years existence of lupus, but afterwards did
not increase anymore. The SDI was significantly higher in patients who
are older then 50 years at the time of diagnosis. The most frequent
damages are valvulaopathies (16,81%); cognitive dysfunction
(14,29%); angina pectoris (13,17%) and venous thrombosis
(13,17%). Higher cummulative steroid dose and using of cyclophosphamide significantly increas the SDI, while hydroxychloroquin treatment is favourable for the patients.
Conclusion: Our data confirm that the most common chronic organ
damages occur in the cardiovascular or neuro-psychiatric system.
Regular follow-up, screening and treatment of these complications
are important.
Lupus
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A065
A066
JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS (JSLE) IN A

TERZIARY CENTRE OF PEDIATRIC RHEUMATOLOGY
(FEATURES, MORBIDITY AND MORBILITY)
Pontikaki I., Becciolini A., Gattinara M., Meroni P.L. and Gerloni V.
Department of Rheumatology, Pediatric Rheumatology Unit, Istituto
Ortopedico G. Pini, University of Milan, Italy
LATE ONSET SYSTEMIC LUPUS ERYTHEMATOSUS:

RETROSPECTIVE STUDY ABOUT 22 CASES
Mezalek Tazi Z.1,2, Maamar M.1,2, Bachir H.1,2, Ammouri W.1,
Harmouche H.1 and Adnaoui M.1,2
1
Universite Mohamed V, Souissi, Faculte de Medecine et de Pharmacie,
Rabat, Maroc 2Internal Medicine departement, Ibn Sina University
Hospital, Rabat, Morocco
Introduction: the clinical and serological features have been analysed in

70 patients with jSLE(< 18 years).
Aim: to evaluate features, morbidity and morbility of jSLE.
Patients and Methods: the mean age of onset was 13 years; 18 patients
were 12 years old or less. The mean duration of disease was 9 years.
Results: there were 3 deaths. The estimated overall survival at 5 years
was 97.9%, at 10 years 93.3% and at 15 years 82.3%. Clinical evidence
of nephritis (proteinuria) occured in 30 patients (42.8%). 23 patients
had 1 or more renal biopsies: 17 (73.9%) resulted affected by diffuse
proliferative glomerulonephritis, 3 (13.0%) by focal proliferative glomerulonephritis and 2 (8.6%) by membranous nephropathy. Out of 28
patients with renal involvement, followed for one year or more, 10
(35.7%) showed arterial hypertension, 5 (17.8%) renal failure, 3
required dialysis. CSN involvement occurred in 9 patients (12.8%): 5
seizures and 4 psychosis, 8 cases out of 9 recovered without permanent
CNS residue. Cutaneous vasculitic lesions, observed in 22 patients
(31.4%), were an important cause of morbidity. Infections remain a
major problem in morbidity: serious infective manifestations occurred
in 15 (21.4%).
The most common organ involvement was skeletal: non erosive arthritis, observed in 61 patients (87.1%) all of whom but one recovered
with restitutio ad integrum; avascular necrosis of bone, observed in 5
cases (7.1%), which required total hip joint replacement in 1 patient;
growth failure and osteoporosis, resulting from prolonged corticosteroid treatment in chronically active disease, were unfrequent but severe
complications in our jSLE series. Short stature, cushingoid features,
striae rubrae and alopecia were frequent problems, due to disease itself
and/or its treatment, that caused increased psychological distress, particularly in adolescents.
Conclusions: these data show that jSLE is not necessarily associated
with poor prognosis; survival has improved, but morbidity due to disease itself and complications of therapy remain a significant problem.
Objectives: Systemic lupus erythematosus (SLE) is a multisystem

inflammatory disease predominantly occurring in females of childbearing age. This disease is uncommon after the age of 50 years and has
different clinical and laboratory characteristics.
Method: We conducted a retrospective study to analyze characteristics
and outcome of patients with late-onset SLE in a Moroccan tertiary
referral center and compare them with those of younger patients with
SLE.
From 1996 to 2012, 22 patients were identified as having late onset
SLE defined as SLE diagnosed at or over the age of 50 years. These
patients were compared with a group of 337 patients aged younger
than 50 years at SLE diagnosis. We compared clinical characteristics,
laboratory data, therapy and outcome.
Results: The female to male ratio is 4.5; mean age at disease onset is
59.5 6 years (51- 78 years). Articular involvement is the most frequent lupus-related symptom present in 95 % cases, followed by cutaneous manifestations in 90 % cases. Renal involvement was noted in 7
cases (glomerulonephritis class III in 4 cases and class IV in 3 cases).
Some manifestations occurred less frequently in late onset SLE ;
nephropathy (28.5 vs 46.8% p<0.005), auto-immune hemolytic
anemia (19% vs 37.2% p <0.005) and lymphopenia (66.7% vs
81.7%). Serositis and thrombopenia occurred more frequently
(42.8% vs 26.7% and 38 vs 28% respectively). Antinuclear antibodies
are present in 96%, anti-DNA antibodies in 71.4% and anti-Sm dans
28.5%. Anti-phospholipid antibodies are present in five patients. There
was no difference between the two groups for the immunological data.
SLE was associated with Biermer disease in two cases, thyroiditis in
one case. One patient has hepatitis C viral cirrhosis and two patients
have myelodysplastic syndrom. Steroids were administrated in eighteen
as oral prednisone between 0.5 and 1 mg/kg per day preceded by a
pulse of methylprednisolone in 2 cases. Hydroxychloroquine was administrated in all cases. Three patients received immunosuppressive
drugs. Two patients died of septic shock. The 5 years overall survival
was 90.4% versus 94.5% in early-onset SLE.
Conclusion: The clinical pattern of late onset is characterized by a lower
disease severity especially with regard to renal involvement. Prognosis
is related to comorbidities and infectious complications.
Lupus
474
A067
LUPUS PODOCYTOPATHY: A CASE REPORT AND
LITERATURE REVIEW
Thomas K.1, Giannou P.2, Gakiopoulou H.3, Koutsianas C.1,
Deutsch M.1, Petras D.2 and Vassilopoulos D.1
1
2nd Department of Medicine and Laboratory 2Renal Unit,
Hippokration General Hospital 3Department of Pathology, Athens
Medical School, Athens, Greece
Introduction: Nephrotic syndrome is usually seen in class IV or V lupus
nephritis. Recently, a number of cases of SLE patients presenting with
nephrotic syndrome and renal biopsy findings consistent with minimal
change disease or focal segmental glomerulosclerosis (FSGS) have
been reported under the term lupus podocytopathy. We report a
case reviewing all cases reported in the English literature.
Case description. A 31-year-old male with history of arthritis (elbows,
wrists) presented with abrupt onset of lower extremities edema.
Laboratory work-up revealed positive ANA (1:2,500), RF, anti-RNP
and anti-Ro antibodies, nephrotic range proteinuria (10 gm/24h),
hypoalbuminemia (1.6 mg/dL), hyperlipidemia, mildly impaired renal
function (Cr1.5 mg/dL) and low C4. A renal biopsy showed in 3/18
glomeruli a tip lesion type FSGS and acute tubular injury. IF was
positive only for IgM (1/4 glomeruli, EM not yet available). The
patient was treated with 3 daily IV methylprednisolone pulses (1 gm)
followed by corticosteroids (CS) pos and azathioprine (2 mg/Kg). 51
cases of lupus podocytopathy were identified in the English literature over the last 20 years (Medline search through PubMed). 87%
were female (mean age 31.6 years) with a median disease duration of
2.5 months. Arthritis (73%) and rash (62%) were common.
Laboratory findings included: ANA (88%), anti-dsDNA (96%),
low C3/C4 (40%), hematuria (46%) and elevated creatinine (43%).
Renal biopsy showed podocyte effacement (97%), mesangial deposits
by IF or EM (70%) and glomerular sclerosis (1 glomeruli, 40%). 29/
43 patients (67%) were treated with CS alone: 20 (69%) showed complete/partial remission, 6 (21%) relapsed and 3 (10%) progressed to
end stage renal disease. 14 patients (33%) were treated with CS and
another agent (MMF, CYC, CsA) with 11 showing complete or partial
remission.
Conclusion: Lupus podocytopathy is an uncommon cause of nephrotic
syndrome in SLE patients. Kidney biopsy is essential for diagnosis
while steroids alone can induce remission in the majority of patients.
A068
OUTCOME OF LONG-STANDING PRIMARY
ANTIPHOSPHOLIPID SYNDROME: A SINGLE CENTER
EXPERIENCE
Taraborelli M.1, DallAra F.1, Reggia R.1, Andreoli L.1, Frassi M.2,
Taglietti M.2, Franceschini F.2 and Tincani A.1
1
Spedali Civili and University of Brescia, Rheumatology and Clinical
Immunology, Brescia, Italy 2Spedali Civili of Brescia, Rheumatology and
Clinical Immunology, Brescia, Italy
Introduction:
Acute
manifestations
related
to
Primary
Antiphospholipid Syndrome (PAPS) are well known, but data on
long-term outcome are still very limited.
Aim: Aim of this study was to describe the outcome of patients with
long-standing PAPS.
Patients and methods: Medical records of patients prospectively followed in our center for at least 15 years were retrospectively reviewed.
Results: Thirty-five Caucasian patients (33 female,2 male) with diagnosis of PAPS [1] followed from 1984 to 2013 with a mean age of 32
years and a median follow-up of 20.5 years (range 15-30) were
included. A thrombotic event appeared in 28% of patients during
follow up (venous 50%, arterial 40% and both 10%). Nineteen
patients (57%) had 28 pregnancies, that were successful in 75% of
cases. Hemorrhagic, infective, neoplastic events were recorded in

34%, 6% and 9% respectively. Organ damage was present in 20%
of patients (17% neurological and 3% renal) and was significantly
associated to the occurrence of thrombotic events (p:0.027) in particular arterial (p<0.001). One patient with chronic bowel ischemia died
for sepsis. No significant variations were observed between the onset
and follow-up for systemic involvement, serological alterations but for
cardiovascular risk factors (less estroprogestinic use p:0.002) and therapy (more hydroxicloroquine p<0.001, immunosuppressants p:0.055
and anti-hypertensive p:0.006).
Conclusions: Despite therapy a high proportion of patients experiences
new thrombotic events and severe complications. Pregnancy outcome
is quite good. Organ damage progresses in a significant proportion of
patients and it is associated with previous arterial events. Unluckily
PAPS can be mortal. A strict control of risk factors and effective treatment are needed to improve the long term outcome.
References
1 Miyakis S et al. International consensus statement on an update of
the classification criteria for definite antiphospholipid syndrome
(APS).J Thromb Haemost 20064(2):295-306.
A069
POOR SLEEP QUALITY IN SYSTEMIC LUPUS
ERYTHEMATOSUS: DOES IT DEPEND ON DEPRESSION?
Tani C.1, Palagini L.2, Carli L.1,4, Signorini E.2, Vagnani S.1,
Querci F.1, Gemignani A.2, Ciapparelli A.2, Bruno R.M.3, Ghiadoni L.3,
Bombardieri S.1 and Mosca M.1
1
Medicine, 2Department of Psychiatry, Neurobiology, Pharmacology and
Biotechnology 3Hypertension Unit,Department of Clinical and
Experimental Medicine, University of Pisa, Italy
Introduction: Sleep disturbances are frequently observed in patients
with rheumatic diseases and significantly affect their quality of life.
The prevalence and characteristics of sleep disturbances in Systemic
Lupus Erythematosus (SLE) have been rarely studied.
Objectives: This study aimed at evaluating the prevalence of insomnia
and poor sleep quality and the determinants of sleep quality in a cohort
of SLE patients.
Patients and Methods: Eighty-one consecutive SLE female patients
were evaluated in a cross-sectional study. The Pittsburgh Sleep
Quality Index (PSQI), the Insomnia Severity Index (ISI), the Beck
Depression Inventory (BDI) and the STAI-Y2 were administered.
Poor sleep quality was defined as PSQI >5, insomnia as ISI >8,
depressive symptoms as BDI > 10, and trait anxiety as STAIY2 > 40. Patients with other sleep disorders were excluded. Fiftythree women with hypertension (without SLE) were enrolled as control
group (H).
Results: In the SLE cohort poor sleep quality was more prevalent than
in H (62.2% versus 39.6%, p<0.01), as well as difficulty in maintaining sleep and/or early morning awakening (62.2% vs 22.9 %,
p<0.001), while insomnia was similarly prevalent (29.7% vs 22.6%,
pns). A depressive disorder was observed in 35.1% of SLE vs 13.3 %
H patients (p<0.001) while anxiety disorders were more common in H
patients (H 35.8% vs SLE 16.2%, p<0.01). SLE was associated with
higher risk of having poor sleep quality (OR. 2.5 [Cl 1.21-5.16]). After
adjusting for confounders, sleep disorders had a significant association
with depression (OR. 6.9 [Cl 1.07-23.6]), while no correlations were
observed with disease duration, activity, damage.
Conclusions: In a cohort of SLE women, insomnia and poor sleep
quality, especially difficulty in maintaining sleep, were common.
Depressive disorders might be responsible for the higher prevalence
of poor sleep quality in SLE.
Lupus
475
A070
A071
PULMONARY ARTERIAL HYPERTENSION IN PATIENTS

WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN MOLDOVA
LUPUS STUDY
Cebanu M.1, Mazur M.1, Mazur-Nicorici L.1, Sadovici V.1, Pasali M.1
and Bartos D.2
1
State University of Medicine and Pharmacy N. Testemitanu,
Republic of Moldova, 2University of Medicine C. Davila, Romania
SEROLOGICALLY ACTIVE CLINICALLY QUIESCENT

SYSTEMIC LUPUS: RESULTS FROM THE PORTUGUESE
REGISTRY REUMA.PT/LES
Santos M.J.1,2, Goncalves M.J.2,3, Ines L.4, Nero P5, Oliveira M.6,
Cerqueira M.7, Sousa S.1, Romao V.2,3, da Silva J.A.P.4 and
Canhao H.2,3
1
Hospital Garcia de Orta, Almada 2Rheumatology Research Unit,
Instituto de Medicina Molecular 3Hospital de Santa Maria, Lisboa
4
Hospitais da Universidade de Coimbra, Coimbra 5Hospital Egas Moniz,
Lisboa 6Centro Hospitalar Cova da Beira, Covilha 7Hospital Conde de
Bertiandos, Ponte de Lima. Portugal
Introduction: Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) which is associated
with a significant risk of death [1]. The data of incidence of PAH in
SLE are controversy.
Objectives: To estimate the incidence of PAH in SLE patients and to
identify the correlation with disease activity.
Methods: A prospective study of 76 patients, who fulfilled Systemic
Lupus International Collaborating Clinics (SLICC, 2012) classification
criteria for SLE, that were recruited from rheumatologic department
between November 2012 and December 2013. Evaluation of pulmonary artery pressure and cardiac morphology was performed at rest with
Transthoracic Doppler Echocardiography as a screening tool. PAH
was defined as systolic pulmonary artery pressure (sPAP)>30mmHg.
The activity of disease was estimated by Systemic Lupus Disease
Activity Index (SLEDAI) and Systemic Lupus Activity Measure
(SLAM).
Results: From 76 patients who entered in the study 73 were female
(92,1%) with median age 44 (12) years, mean SLICC criteria
number 6,25 (1,65), range 4-10, mean disease duration - 7,2 (
6,9) years, range 1-360 months. The activity of SLE by SLEDAI was
12,76 (8,9) and by SLAM - 13,55 (5,8) points. Seven patients (2,7%)
were found to have PAH with sPAP>30mmHg, among them 4
patients had 32 40mmHg, 2 patients had 40 45mmHg and there
was just one patient with 70mmHg. There was a significant correlation
between PAH and SLAM (r0,6, p<0,001) but no correlation with
SLEDAI (r0,009, p 0,9572) was observed. PAH was moderately
associated with duration of disease r0,4, p<0,05.
Conclusion: The incidence of PAH in our study was 2,7% and the
majority were with moderate severity. A significant correlation was
observed between PAH and SLAM that may confirm its sensibility
versus SLEDAI.
Introduction: The majority of patients with systemic lupus erythematosus (SLE) is clinically and serologically concordant, but in some
cases, high titers of anti-dsDNA antibodies and/or hypocomplementemia persist in the absence of clinical manifestations. The implications
of isolated serological activity are not fully understood and there is no
consensus on the best therapeutic approach for this particular group of
patients.
Aim: To identify the frequency and characterize patients with serologically active clinically quiescent (SACQ) SLE.
Patients and methods: Patients with the diagnosis of SLE followed in
the Portuguese registry Reuma.pt/LES and SLEDAI-2K of 2 or 4 due
to hypocomplementemia and/or positive anti-dsDNA antibody titers
in at least 2 consecutive visits at >3 months interval were included.
Results: Of the 640 patients with 2 visits registered in Reuma.pt/LES,
55 (8.6%) fulfilled the inclusion criteria. The median duration of
SACQ-SLE period was 140 [98-294] days. 23 (42%) are treated with
antimalarials or no medication (Group 1) while the remaining 32 are
medicated with corticosteroids and/or immunosuppressive drugs
(Group 2).
The prevalence of auto-antibodies (anti-Sm, anti-Ro, anti-La, antiRNP or aPL) is similar between groups.
Conclusions: In this large Portuguese lupus cohort, SACQ is uncommon. Using the stricter definition (Group 1) SACQ-SLE was found in
only 23 patients. No clinical or immunological differences could be
identified between SACQ patients receiving corticosteroids and/or
immunosuppressants and those receiving only antimalarials.
Table 1.
References
1 Prabu A., et al. Prevalence and risk factors for pulmonary arterial
hypertension in patients with lupus. Rheumatology Oxford Journals
2009; 48: 15061511.
Characteristics
Group 1 (n23)
Group 2 (n32)
p-value
Age (years)
Female (%)
Caucasian (%)
Disease duration (years)
Previous involvement:
- renal (%)
- neuropsychiatric (%)
- hematologic (%)
SLICC-DI 1 (%)
41.62.3
87.0
95.7
12.61.4
43.43.1
96.9
76.7
11.01.7
0.556
0.298
0.159
0.236
27.3
4.8
68.2
21
30.2
3.3
56.7
14.8
1.000
1.000
0.565
0.860
Lupus
476
A072
A073
SYSTEMIC LUPUS ERYTHEMATOSUS PRESENTING AS

SEVERE RELAPSING NEUROMYELITIS OPTICA
Avdikou M.1*, Karageorgas T.2*, , Markoulaki D.1, Nousia O.1,
Kalogeromitros A.1, Lintzeri A.2, Boumpas D.T.3 and
Papakonstantinou K.1
*Equal contribution. 1General Hospital of Athens G.Gennimatas,
Intensive Care Unit, Athens, Greece 2General Hospital of Athens
G.Gennimatas, Rheumatology Department, Athens, Greece 3National
and Kapodistrian University of Athens, Medical School, Athens, Greece
THE IMPAIRMENT OF LEFT VENTRICULAR SYSTOLIC

PERFORMANCE IN SYSTEMIC LUPUS ERYTHEMATOSUS
Pamfil C.1, Gusetu G.1, Flestea A.2, Mardale M.1, Pop D.1,
Zdrenghea D.1 and Rednic S.1
1
Iuliu Hatieganu University, Cluj, Romania 2Babes-Bolyai University,
Cluj, Romania
Introduction: Neuromyelitis optica (NMO) has been associated with

Systemic Lupus Erythematosus (SLE) occasionally representing the
initial manifestation of the disease.
Case Description: A 57 year-old female patient on azathioprine and
prednisolone for recurrent episodes (n 6) of NMO (aquaporin-4 antibody positive) presented with dry cough, dyspnea and fever (39oC) and
progressively deteriorating weakness of all four limbs over the past
month. On examination she had dyspnea at rest and flaccid paralysis
with absent reflexes of the upper limbs and decreased muscle strength
(2/5) with hypertonia and brisk reflexes of the lower limbs. Synovitis of
the wrist, metacarpophalangeal and metatarsophalangeal joints, malar
rash, erythematous rash of the neck and upper back were also detected.
Mechanical ventilation was required due to acute respiratory failure.
Chest CT scan showed bilateral lower lobe infiltrates with pleural and
pericardial effusion. Blood test results revealed leucopenia, ANA>1/
1280, anti-dsDNA positive and low levels of C3 and C4. A complete
work up for infections yielded negative results. Cerebrospinal fluid
analysis showed pleocytosis (>600cells/mm3, 70% neutrophils), protein of 990mg/dL and normal glucose concentration. Brain and spine
MRI scan reported multiple hyperintense (in T2-FLAIR weighted imaging) non-enhancing lesions in the medulla, pons, cerebellum, midbrain, corona radiata and centrum semiovale. Moreover hyperintense
lesions were detected in T2-STIR weighted images from the medulla to
T7 level with mildly enhancing lesions at the level of T5, T6 and T7
(Figure) consistent with acute myelitis. She received iv methylprednisolone and IVIg for five consecutive days with resolution of the pulmonary infiltrates and serositis and stabilization of the neurologic
disease to be followed by Rituximab.
Conclusion: Patients diagnosed with NMO should be screened by a
rheumatologist for an underlying systemic autoimmune disease (SLE
or Sjogrens syndrome) as neurologists may miss subtle evidence of
these diseases.
Introduction: Cardiovascular disease is increasingly acknowledged as a

main cause of mortality and morbidity in systemic lupus erythematosus (SLE). Ultrasonography allows accurate evaluation of the myocardium, which damaged may contribute to impaired functional capacity
of patients with SLE.
Aim: To assess the presence of myocardial systolic impairment in
patients with SLE by 2D echography and speckle-tracking strain analysis and to investigate its relationship to immunological and clinical
features in SLE patients.
Patients and Methods: Thirty-eight asymptomatic SLE patients (mean
age 44 5.9 years, 81% female) and 20 matched healthy controls
underwent transthoracic echocardiography (chamber diameters,
LVEF, valve abnormalities and LV systolic performance by speckle
tracking imaging). In LES patients, clinical data, disease activity and
damage scores were additionally obtained.
Results: Out of the 38 patients, 31% had mild mitral regurgitation and
one patient (2%) had mild aortic regurgitation. Increased values of
pulmonary systolic pulmonary arterial pressure suggestive for pulmonary hypertension were recorded in 23% in SLE patients, the majority
categorized as mild. Standard 2D measurements were similar in both
groups, but global longitudinal strain (GLS) was significantly reduced
in the SLE group (19.15 1.21 % vs. 20.45 1.49 %, p0.045). No
significant correlations between age and GLS were observed in neither
groups. Furthermore, disease duration did not correlate with GLS.
GLS values were lower in patients with associated antiphospholipid
syndrome (APS) (18.5 1.03 % vs 19.6 0.63 %, p0.038). No correlation between the presence of standard cardiovascular risk factors
and GLS values in patients with SLE was observed.
Conclusion: There is a significant impairment of the systolic myocardial
performance, which doesnt result from the presence of known CV risk
factors, but which correlates with APS and damage accrual. These
findings support the usefulness of an early and accurate ultrasound
assessment of the heart in order to improve the morbidity and mortality among SLE patients.
A074
THE NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC
LUPUS - A MONOCENTRIC STUDY OF 95 CASES
Tazi Mezalek Z.1,2, Bachir H.1, Ammouri W.1, Maamar M.1,2,
Harmouche H.1,2 and Adnaoui M.1,2
1
Rabat, Maroc 2Internal Medicine departement, Ibn Sina University
Introduction:The neuropsychiatric manifestations are one of the the
most deadful manifestations of systemic lupus erythematosus (SLE).
The purpose of this study is to analyze the clinical and biological features, evolution and related factors of neuropsychiatric complication of
SLE.
Patients Methods: Its a retrospective monocentric study of 348 cases
diagnosed between 1990 and 2010 in an internal medicine department,
using ACR criteria.
Results: The neuropsychiatric manifestations were observed in 95 cases
(27.3%) mostly in women (95%). The average age was 3011 years.
The neurological disorders were inaugural in 85%. The central
Lupus
477
neurological manifestations (83%) were: convulsions in 24 patients
(25.2%), psychotic troubles in 23 (24.2%), headaches in 40 (42.1%),
aseptic meningitidis in 7 (7.3%), ischemic stroke in 6 (6.4%), vascularitis and myelopathy in 5 patients each (5.2%) and thrombophlebitis in
2 (2.1%). The peripheral neurological manifestations (17%) were peripheral neuropathy in 12 patients (12.6%), cranial nerve involvement
in 5 (5.2%) and acute polyradiculoneuropathy in 4 (4.1%). The antinuclear antibody were positive in 93 (97.3%) patients, the DNA antibody in 78 (82.1%) and the anticardiolipin antibody in 19 (20%). The
factors significantly associated with neurological events were: a high
SLEDAI score (P< 0.001), thrombocytopenia (p0.002), leukopenia
(p0.05) and an anti phospholipid syndrome (P0.028).
All patients were treated with corticosteroids, 98% with antimalarial
and 52 (54.7%) with immunosupressive agents. The evolution was
good in 51 patients (53%) but a relapse was observed in 34 (35.8%).
Ten (10.5%) patients deceaded mostly by infectious complications
(P< 0.001).
Conclusion: In our report, neurological manifestations were frequent
and associated with poor prognosis.
A075
ULTRASOUND EVALUATION OF WRIST AND HAND IN
SYSTEMIC LUPUS ERYTHEMATOSUS
Popov H.I.1, Tamas M.M.1,2, Pamfil C.1,2, Rnzis M.1 and Rednic S.1,2
1
Emergency County Clinical Hospital, Department of Rheumatology
2
Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca,
Romania
Introduction: To date, few studies evaluated joint and tendon involvement in SLE patients by ultrasonography (US) and the incidence and
the nature of US abnormalities differ among studies.
Aim: To describe and determine the frequency of US abnormalities of
hand and wrist in SLE.
Patients and methods: 35 randomly selected SLE patients were enrolled
in the study. Clinical examination and US evaluation (Gray Scale and
Power Doppler (PD)) of the wrist and hand was performed bilaterally.
20 age-matched healthy subjects were included as controls.
Results: Upon clinical examination, 20% of SLE subjects had arthralgia, and 9% arthritis. US examination revealed abnormalities in 77%
of cases. The most common finding was synovitis in 66% (48% wrist;
13% MCP/PIP, 39% both) with a 2/3 grade in 23% of the cohort. All
patients with clinical arthritis had grade 3 synovitis(3/35); notably, US
detected additional 2/3 grade synovitis in 5 patients. PD abnormalities
were present in 14% of patients, but only 60% of them had synovitis at
time of examination.
Bone erosions were described in 29%, located at the site of the second
and fifth MC heads in two thirds of cases. US identified tenosynovitis
in half of patients, involving the wrist extensors in the vast majority of
cases (81%). Among healthy controls, US abnormalities were detected
in 20% of cases, without any accompanying PD abnormalities or structural damage.
Conclusions: US abnormalities are common in SLE patients. US examination detects significant synovitis of the hand and wrist in the
absence of clinical findings, and reveals structural damage in a large
number of patients. Tendon involvement is frequent and shows a specific pattern: the involvement of wrist extensors. Thus, US may help
aid monitoring of joint disease activity and modulate treatment strategies in SLE patients.
Biomarkers, histopathology and imaging

A076
ANTI-C1Q-ANTI-PTX3 ANTIBODY BALANCE INFLUENCES
NEPHRITIS PROGRESSION IN HUMAN AND MURINE LUPUS
Gatto M.1, Ghirardello A.1, Bassi N.1, Zen M.1, Bettio S.1, Nalotto L.1,
Iaccarino L.1 and Doria A1
Division of Rheumatology, University of Padova, Padua, Italy.
Background: Soluble long pentraxin 3 (PTX3) is an acute phase protein
involved in clearance of complement fragment 1 (C1q). Anti-C1q antibodies are more prevalent and anti-PTX3 less prevalent among SLE
patients developing lupus nephritis (LN).
Aim: To assess the link between serum anti-PTX3 and anti-C1q antibodies, renal PTX3 and LN in SLE patients, and to test whether antiPTX3 antibodies are protective against LN in murine lupus.
Materials and Methods: Levels of anti-PTX3 and anti-C1q antibodies
were measured on sera of 130 consecutive SLE patients by home-made
ELISA. PTX3 deposition was evaluated on 29 biopsies by immunohistochemical analysis and kidney fibrosis by Massons staining.
10 NZB/NZW mice were injected with 100 mg PTX3 in 100 ml PBS
(group 1) and 10 NZB/NZW mice with PBS 200 ml (group 2), 3 times 3
weeks apart. Anti-C1q, anti-PTX3 and anti-DNA antibody titers, proteinuria-free survival (300mg/dl) and overall survival were compared.
Two-tailed t test, Fishers exact test and Pearsons correlation test were
performed; mice survival rates were evaluated by Kaplan-Meyer
method using Mantel-Cox for comparison.
Results: Anti-C1q levels were significantly higher and anti-PTX3 significantly lower in patients with LN than non-renal patients
(p<0.0001); a negative association of anti-PTX3 with LN was found
(R20.343, p<0.0001). Prevalence of LN was higher in anti-C1q/
anti-PTX3- than in C1q/anti-PTX3 or C1q-/anti-PTX3- and no
LN was observed in anti-C1q-/anti-PTX3 patients (p<0.0001).
Renal PTX3 deposition was highest in anti-C1q/anti-PTX3- patients
and directly correlated with both proteinuria (r0.47, p0.024) and
kidney fibrosis (r0.49, p0.023).
Anti-PTX3 antibodies appeared only in mice injected with PTX3
(p<0.0001). Group 1 mice developed anti-C1q and anti-DNA antibodies later and at significantly lower titers than group 2 (p0.001).
Group 1 mice displayed significantly longer proteinuria-free survival
and overall survival (p0.008 and p0.024, respectively).
Conclusions: The presence/absence of anti-C1q and anti-PTX3 antibodies may influence the progression of LN in humans. Anti-PTX3 antibodies may hinder LN onset in murine lupus.
References
1 Delle Sedie A, et al. Clin Exp Rheumatol 2009;27:897-901.
2 Gabba A, et al. Rheumatology 2012;51:2278-2285.
Lupus
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A077
BIOMARKERS IN CHILDHOOD-ONSET SYSTEMIC LUPUS
ERYTHEMATOSUS: A SYSTEMATIC REVIEW
Groot N.1,2,3, Avcin T.4, Vastert S.J.1, Bader-Meunier B.5, KonePaut I.6, Pilkington C.7, Ravelli A.8, Kamphuis S.S.M.2 and
Beresford M.W.3
1
Wilhemina Childrens Hospital/UMCU, Department of Pediatrics,
Utrecht, The Netherlands 2Sophia Childrens Hospital/EMC,
Department of Pediatric Immunology, Rotterdam, the Netherlands
3
Alder Hey Childrens NHS FoundationTrust Hospital, Department of
Womens & Childrens Health, Liverpool, United Kingdom 4University
Medical Center, Department of Allergology, Rheumatology, and Clinical
Immunology, Ljubljana, Slovenia 5Necker Hospital, Department of
Pediatric Immunology and Rheumatology, Paris, France 6CHU de
Bicetre, Department of General Pediatrics and Pediatric Rheumatology,
Paris, France 7Great Ormond Street NHS Hospital, Department of
Paediatric Rheumatology, London, UK 8Gaslini Childrens Hospital,
Department of Pediatric Rheumatology, Genova, Italy
Introduction: Childhood-onset systemic lupus erythematosus (cSLE)
represents a more severe phenotype of SLE than adult-onset disease,
and early diagnosis and recognition of complications are especially
important. Biomarkers can help significantly in achieving this.
Aim: A systematic literature review was performed to analyse the usefulness of biomarkers for diagnosis and monitoring of cSLE.
Methods: The search was executed in MEDLINE, EMBASE and
Cochrane. EULAR guidelines for recommendations were used to
assess study validity and level of evidence. A minimum validity score
of moderate and level of evidence of 2B (case controlled studies) was
set for inclusion. This study was part of the SHARE Project (Single
Hub and Access point for paediatric Rheumatology in Europe).
Results: After the initial search, 83 articles on biomarkers in cSLE were
identified. Most studies combined paediatric and adult data. Nine articles regarded pediatric data only and were eligible for analysis. The
following biomarkers were identified: anti-nuclear antibodies (antiNCS, anti-Ro, anti-La, anti-Sm, anti-RNP, anti-ENA, anti-dsDNA,
antichromatin, anti-ENA), protein markers (neutrophil gelatinaseassociated lipocalin), anti-ribosomal antibodies (anti-U1RNP, antiribosomal P) and complement factors (anti-C1q). Table 1 summarizes
the results of the identified studies.
Conclusion: Systematic review of literature identified biomarkers
that could aid in diagnosis and monitoring cSLE disease progression.
Anti-C1q-antibodies are rarely found but are of use in cSLE diagnosis

in anti-dsDNA-negative patients. Specific anti-nuclear antibodies such
as anti-NCS, and NGAL levels are promising biomarkers for monitoring disease activity.
References
1 Malleson P, Tekano J. Diagnosis and management of systemic lupus
erythematosus in children. Paediatr. Child Health (Oxford).
[Internet]. Malleson, P., Division of Pediatric Rheumatology,
University of British Columbia, Rheumatology Service,
Vancouver, Canada; 2008;18(2):619. Available from: http://
www.embase.com/search/
results?subactionviewrecord&fromexport&idL351288608.
2 Dougados M, Betteridge N, Burmester GR, Euller-Ziegler L,
Guillemin F, Hirvonen J, et al. EULAR standardised operating
procedures for the elaboration, evaluation, dissemination, and
implementation of recommendations endorsed by the EULAR
standing committees. Ann. Rheum. Dis. [Internet]. 2004 Sep [cited
2014 Jan 13];63(9):11726. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid1755117
&toolpmcentrez&rendertypeabstract.
3 Wulffraat NM, Vastert B. Time to share. Pediatr. Rheumatol.
Online J. [Internet]. Pediatric Rheumatology; 2013 Jan [cited 2014
Jan 13];11(1):5. Available from: http://www.pubmedcentral.nih.gov/
articlerender.
fcgi?artid3583675&toolpmcentrez&rendertypeabstract.
4 Campos LMA, Kiss MHB, Scheinberg MA, Mangueira CLP, Silva
CA. Antinucleosome antibodies in patients with juvenile systemic
lupus erythematosus. Lupus [Internet]. 2006/09/01 ed. 2006 Jan
[cited 2013 Aug 28];15(8):496500. Available from: http://
www.ncbi.nlm.nih.gov/pubmed/16942001.
5 Hinze CH, Suzuki M, Klein-Gitelman M, Passo MH, Olson J,
Singer NG, et al. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic
lupus erythematosus disease activity. Arthritis Rheum. [Internet].
2009/08/29 ed. 2009 Sep [cited 2013 Aug 27];60(9):277281.
Available
from:
http://www.pubmedcentral.nih.gov/
articlerender.fcgi?artid3064260
&toolpmcentrez&rendertypeabstract.
6 Jesus AA, Silva CA, Carneiro-Sampaio M, Sheinberg M,
Mangueira CL, Marie SK, et al. Anti-C1q antibodies in juvenileonset systemic lupus erythematosus. Ann. N. Y. Acad. Sci.
[Internet]. 2009/09/18 ed. 2009 Sep [cited 2013 Aug 28];1173:235
8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19758156.
7 Jesus AA de, Campos LMA, Liphaus BL, Carneiro-Sampaio M,
Mangueira CLP, Rosseto EA, et al. Anti-C1q, anti-chromatin/
nucleosome, and anti-dsDNA antibodies in juvenile systemic lupus
erythematosus patients. Rev. Bras. Reumatol. [Internet]. 2012/12/12
Table 1.
Author (et al)
Validity
Level of
Evidence
Biomarker
studied
Campos L 2006 (4)

Hinze C 2009 (5)
Valid
Valid
2A
2A
Jesus AA 2009 (6)

Jesus AA 2012 (7)
Jurencak R 2009 (8)
Moderate
Moderate
Valid
2B
2B
2A
Antinucleosome antibodies
Neutrophil Gelatinase-associated
Lipocalin (NGAL)
Anti-C1q Antibodies
Anti-C1q Antibodies
Spectrum of autoantibodies
Lehman TJ 1980 (9)

Tang X 2010 (10)
Moderate
Valid
2B
2B
anti-dsDNA
Spectrum of autoantibodies
Wu F 2011 (11)
Moderate
2B
Anti-C1q and Anti-C1q Antibodies
Wu JF 2006 (12)
Valid
2B
Antinucleosome (anti-NCS) antibodies
Results
Correlates with malar rash, haemolytic anemia, SLEDAI-score
NGAL levels may be of use in predicting global and renal cSLE
disease activity
Despite low occurrence, a good marker for cSLE diagnosis.
anti-C1q Ab is useful in cSLE diagnosis if anti-dsDNA is negative
Antibody clusters correlate with different disease manifestations:
Cluster 1: anti-dsDNA; Cluster 2: anti-dsDNA, antichromatin,
antiribosomal P, anti-U1RNP, anti-Sm, anti-Ro, antiLa; Cluster 3: anti-dsDNA, anti-RNP, anti-Sm anti-dsDNA
Anti-dsDNA is highly specific for SLE
Distinct serologic and clinical correlations with autoantibody clusters are shown in South Chinese cSLE
Levels of C1q and C1qAb correlate with severity of cSLE and could
be of use in diagnosis of nephritis
anti-NCS Ab had high cSLE sensitivity and specificity. Levels correlated with SLEDAI score
Lupus
479
ed. 2012 Dec [cited 2013 Aug 28];52(6):97681. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/23223707.
8 Jurencak R, Fritzler M, Tyrrell P, Hiraki L, Benseler S, Silverman
E. Autoantibodies in pediatric systemic lupus erythematosus: ethnic
grouping, cluster analysis, and clinical correlations. J. Rheumatol.
[Internet]. 2009/02/12 ed. 2009 Feb [cited 2013 Aug 28];36(2):416
21.
Available
from:
http://www.ncbi.nlm.nih.gov/pubmed/
19208567.
9 Lehman TJ, Hanson V, Singsen BH, Kornreich HK, Bernstein B,
King K. The role of antibodies directed against double-stranded
DNA in the manifestations of systemic lupus erythematosus in
childhood. J. Pediatr. [Internet]. 1980/04/01 ed. 1980 Apr [cited
2013 Aug 28];96(4):65761. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6965717.
10 Tang X, Huang Y, Deng W, Tang L, Weng W, Zhang X. Clinical
and serologic correlations and autoantibody clusters in systemic
lupus erythematosus: a retrospective review of 917 patients in
South China. Medicine (Baltimore). [Internet]. 2010/01/16 ed.
2010 Jan [cited 2013 Aug 28];89(1):627. Available from: http://
www.ncbi.nlm.nih.gov/pubmed/20075706.
11 Wu FQ, Zhao Q, Cui XD, Zhang W. C1q and anti-C1q antibody
levels are correlated with disease severity in Chinese pediatric systemic lupus erythematosus. Rheumatol. Int. [Internet]. 2009/12/25
ed. 2011 Apr [cited 2013 Aug 28];31(4):5015. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/20033414.
12 Wu J-F, Yang Y-H, Wang L-C, Lee J-H, Shen E-Y, Chiang B-L.
Antinucleosome antibodies correlate with the disease severity in
children with systemic lupus erythematosus. J. Autoimmun.
[Internet]. 2006/08/22 ed. 2006 Sep [cited 2013 Aug 28];27(2):119
24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/
16919912.
A078
BLYS AND APRIL IN LUPUS NEPHRITIS: CORRELATIONS
WITH SEROLOGY - BLYS AS A NON-INVASIVE PREDICTOR
OF RESPONSE
Parodis I.1, Zickert A.1, Axelsson M.2, Svenungsson E.1, Malmstrom V.1
and Gunnarsson I.1
1
Department of Medicine, Rheumatology Unit, Karolinska Institutet,
Stockholm, Sweden 2AlbaNova, Stockholm University, Stockholm,
Sweden
Introduction: Lupus nephritis (LN) affects up to 50% of patients with
Systemic Lupus Erythematosus (SLE). The B-lymphocyte is pivotal in
SLE and autoantibody production. B-lymphocyte stimulator (BLyS)
and a proliferation-inducing ligand (APRIL) are important for the
activation and maintenance of B-cells.
Aim: We investigated serum levels of BLyS and APRIL in patients with
LN to clarify how these levels are affected by conventional immunosuppression. Through comparison with clinical data and correlation
with autoantibodies, we further aimed to evaluate BLyS and APRIL as
potential biomarkers for LN in comparison to conventional serology.
Patients and Methods: Sixty-four patients with active biopsy-ascertained LN (52 proliferative LN, PLN; 12 membranous LN) and 64
individually matched controls were included. After induction therapy a
follow-up biopsy was performed. Serum samples at baseline and
follow-up were analyzed for BLyS, APRIL, autoantibodies and complement levels. Clinical response (CR) was defined as 50% reduction
in proteinuria, normal or improved renal function and inactive urinary
sediment.
Results: Comparing patients to controls, baseline BLyS levels were
significantly higher in patients (p<0.001) and remained unchanged
after treatment. APRIL levels were significantly higher in patients at
baseline (p0.005), but not at follow-up. Among PLN patients, the
decrease of APRIL was significant only in responders (p0.009 for

CR). Significant decreases of anti-dsDNA (p<0.001) and anti-C1q
(p<0.001) were observed in PLN patients. Low baseline BLyS levels
(<1.5 ng/mL) predicted treatment response, attaining a positive predictive value of 92% for CR among PLN patients.
No correlation was found between BLyS/APRIL and anti-dsDNA,
anti-C1q, C3 or C4, at either baseline or follow-up. However, significant correlations were found between BLyS and anti-dsDNA in the
combined patient group (rs0.47, p<0.001), and among PLN patients
(rs0.49, p<0.001).
Conclusions: Our results indicate that APRIL is of importance in PLN,
and stress the need to evaluate BLyS as a candidate non-invasive prognostic biomarker of treatment response in LN.
A079
DYNAMIC SUSCEPTIBILITY CONTRAST MAGNETIC
PERFUSION IMAGING (DSC-MRI) TECHNIQUE IN
NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS
(NPSLE): DIFFUSE HYPOPERFUSION IN NORMAL
APPEARING WHITE MATTER (NAWM) AND DEEP GRAY
MATTER (DGM)
Papadaki E.1, Fanouriakis A.2, Kavroulakis E.1, Bertsias G.2,
Sidiropoulos P.2, Maris T.3, Boumpas D.T.2 and Karantanas A.1
Departments of 1Radiology, 2Rheumatology and 3Medical Physics,
University Hospital of Heraklion, Greece
Introduction: PET and SPECT studies revealed hypometabolism and
hypoperfusion in NAWM and DGM regions in NPSLE patients (1, 2),
but have limited anatomic resolution and high-radiation dose. The
DSC-MRI technique is widely used for the detection of hemodynamic
changes in CNS diseases, but its application in NPSLE is still very
limited (3).
Aim: To investigate possible hemodynamic impairment in NPSE
patients, using DSC-MRI.
Patients and Methods: 25 NPSEL patients, 20 SLE patients without
CNS involvement (SLE-controls) and 25 healthy volunteers (HV) were
administrated brain MRI studies. The DSCI-MRI technique was
applied and regional cerebral blood volume (CBV), cerebral blood
flow (CBF), and mean transit time (MTT) values were estimated in
20 regions of interest (ROIs), placed in NAWM and DGM structures
bilaterally. Group differences on perfusion values were assessed using
one-way ANOVAs, separately for each ROI and evaluated at
Bonferroni-adjusted a 0.05/20 (ROIs) 0.0025.
Results: NPSLE patients had lower CBF values and higher MTT
values than HV, across all 20 ROIs, but higher CBV values only in
NAWM. Compared to SLE-controls, NPSLE patients had lower CBF
values in DGM and higher MTT values in NAWM and DGM. Lower
CBF values in NPSLE patients, as compared to SLE-controls, reached
significance in periventricular NAWM and semioval center. There was
no significant difference in CBF, CBV, and MTT values between SLEcontrols and HV.
Conclusions: NPSLE patients are characterized by diffuse significant
hypoperfusion in DGM compared to SLE- control patients and HV,
and hypoperfusion in NAWM compared to HV. There is no significant
hemodynamic differences between SEL- control patients and HV.
References
1 Appenzeller S et al. Rheumatology 2007; 46:467472.
2 Otte A et al. Eur J Nucl Med 1997; 24:78791.
3 Emmer BJ et al. J Magn Reson Imaging 2010;32:283288.
Lupus
480
A080
and HSP. Further assessment in a larger, prospective paediatric cohort

is warranted.
IDENTIFYING FUTURE URINARY BIOMARKER TARGETS

FOR MONITORING OF LUPUS NEPHRITIS DISEASE
ACTIVITY
Smith E.1, Midgley A.1, Watson L.1, Jones C.3, Pilkington C.4,
Marks S.D.5, Tullus K.5 and Beresford M.W.1,6
1
Institute of Translational Medicine, University of Liverpool, Liverpool,
UK. 3Department of Nephrolology, Alder Hey Childrens Hospital,
Liverpool. 4 Paediatric Rheumatology Department, Great Ormond
Street Hospital for Children Hospital, London, UK. 5 Nephrology Unit,
Great Ormond Street Hospital, London. 6 Department of Rheumatology,
Alder Hey Childrens Hospital, Liverpool.
References
1 Watson L, Leone V, Pilkington C, et al. Disease activity, severity,
and damage in the UK Juvenile-Onset Systemic Lupus
Erythematosus Cohort. Arth Rheum 2012; 64(7235665.
2 Hagelberg S, Lee Y, Bargman J, et al. Long-term follow-up of
childhood lupus nephritis. J Rheumatol 2002; 29(12263542.
3 Levy M, Montes de Oca M, Claude-Babron M. Unfavorable
outcomes (end-stage renal failure/death) in childhood onset systemic
lupus erythematosus. A multicenter study in Paris and its environs.
Clin Exp Rheum 1994; 12(Suppl 10S638.
Introduction: Up to 80% of children with juvenile-onset systemic lupus

erythematosus (JSLE) develop lupus nephritis (LN) (1), with between
4-44% progressing to end stage renal disease (2,3).
Aim: To identify novel urinary protein biomarker targets to facilitate
development of a point of care testing device for monitoring LN disease activity.
Patients and methods: The relative expression of 38 urinary proteins
was analysed using a kidney biomarker proteome profiler array (R&D
systems Ltd). Samples from JSLE patients (n4) participating in the
UK JSLE Cohort study with active LN (renal domain British Isles
Lupus Assessment Group (BILAG) score of A or B) were compared
to age and sex matched healthy controls (HC, n2), and renal inflammatory control patients (Henoch-Schonlein-Purpura, HSP, n2).
Results: All JSLE patients (n4) with active LN displayed a 2-fold
increase in the expression of chemokine ligand 16 (CXCL16), monocyte chemoattractant protein (MCP-1), and thrombospondin-1 as
compared with HC. 75% of patients with active LN displayed a 2fold increase in the expression of: tumor necrosis like weak inducer of
apoptosis (TWEAK), matrix metalloprotease-9 (MMP-9), annexin V,
epidermal growth factor receptor (EGF R), chemokine ligand 1
(CXCL1), prostate specific antigen (PSA), vascular endothelial
growth factor (VEGF), receptor for advanced glycation end products
(RAGE), resistin and tumor-necrosis-factor receptor-1 (TNFR1), as
compared with HC (Table 1). Active LN patients displayed a higher
expression of MMP9, IL-1ra, annexin V and TWEAK than active HSP
patients.
Conclusions: This preliminary analysis has shown a number of novel
urinary proteins to distinguish between patients with active LN, HC
Table 1. Relative fold differences in urinary protein expression between
JSLE patients and healthy controls
Fold differences in urinary protein
expression relative to health control
Urinary Proteins
Median fold difference
Interquartile range
CXCL16
MCP-1
Thrombospondin-1
TWEAK
MMP-9
Annexin V
EGF R
CXCL1
PSA
VEGF
RAGE
TNFR1
Resistin
2.7
2.6
3.4
3.5
2.1
2.1
2.5
2.5
2.3
4.5
2.2
2.0
3.7
2.3-7.6
2.4-2.7
2.9-4.1
2.8-3.6
1.8-2.5
1.8-2.4
2.1-3.3
2.1-3.3
1.9-2.6
3.1-5.4
1.8-2.4
1.8-2.2
2.3-5.1
A081
MRI PATTERN OF ARTHRITIS IN SLE: A COMPARATIVE

STUDY WITH RHEUMATOID ARTHRITIS AND HEALTHY
SUBJECTS
Tani C.1, Carli L.1,2, Daniello D.3, Possemato N.1, Cagnoni M.1, Delle
Sedie A.1, Riente L.1, Vagnani S.1, Caramella D.3, Bombardieri S.1 and
Mosca M.1
1
Medicine, University of Pisa, Pisa, Italy 2GenOMEC PhD, University of
Siena, Siena, Italy 3Radiology Unit, University of Pisa, Pisa, Italy
Introduction: Arthritis in systemic lupus erythematosus (SLE) is traditionally considered mild and non erosive, however chronic pain, hand
disability and deformities are frequently reported by patients with
longstanding disease. Magnetic resonance imaging (MRI) has demonstrated to be more sensitive for identifying bone damage than conventional radiography and it is widely used as an outcome measure of joint
damage in rheumatoid arthritis (RA) clinical trials.
Objectives: In this study we aimed at describing the magnetic resonance
imaging (MRI) pattern of distribution of bone marrow oedema (BME)
and joint erosion in hands and wrists of patients with Systemic Lupus
Erythematosus (SLE) with arthritis in comparison with Rheumatoid
arthritis (RA) and healthy subjects (H).
Methods: SLE patients with arthritis (n50), patients with RA (n22)
and H (n48) were enrolled. Every patient underwent a non dominant
hand (2nd5th metacarpophalangeal joints) and wrist MRI without
contrast injection with a low- field extremity dedicated 0.2 Tesla
instrument.
Results: BME was observed in 2 SLE patients at hand (4%) and in 15
at wrist (13%) versus 3 (30%) and 14(63%) RA patients. No BME was
found in H. Erosions were observed at the hand in 24 SLE patients
(48%), 15 RA patients (68%) and 9 H (18%); at the wrist, in 41 (82%)
SLE, all RA and 47 (97%) H. The cumulative erosive burden in SLE
was significantly higher than in H (p0.002) but similar to RA
patients. Distribution of joint erosions at the non dominant hand
and wrist in SLE, RA patients and in healthy subjects is reported in
Table 1.
Conclusions: Joint involvement in SLE can be severe with a significant
tendency to develop BME and erosions, similarly to RA; this condition
is not rare as previously expected.
Lupus
481
Table 1. Distribution of joint erosions at the non dominant hand and wrist in SLE, RA patients and in healthy subjects
II metacarpal head
III metacarpal head
IV metacarpal head
V metacarpal head
II phalangeal base
III phalangeal base
IV phalangeal base
V phalangeal base
Trapezius
Trapezoid
Capitate
Hamate
Scaphoid
Lunate
Triquetum
Pisiform
Radius
Ulna
Basis MC I
Basis MC II
Basis MC III
Basis MC IV
Basis MC V
H (%)
P (SLE vs H)
SLE (%)
P (SLE vs RA)
RA (%)
0
0
0
0
4 (9%)
3 (7%)
0
3 (7%)
4 (8%)
9 (19%)
32 (66%)
9 (19%)
10 (20%)
40 (83%)
28 (58%)
1 (2%)
9 (19%)
7 (14%)
4 (8%)
0
1 (2%)
2 (4%)
0
ns
ns
ns
ns
ns
ns
0.04
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
0.03
0.04
ns
0.05
3
4
3
4
10
10
7
6
6
13
43
20
19
47
37
3
16
13
15
9
7
4
4
0.008
0.006
0.03
ns
ns
0.01
ns
0.003
0.03
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
0.02
0.01
0.04
ns
8
8
5
1
9
12
4
9
10
7
19
12
13
21
20
2
12
6
9
11
11
6
1
A082
PLASMA LEVELS OF PF-4VAR/CXCL4L1, A NON ALLELIC
VARIANT OF PLATELET FACTOR-4 (PF-4/CXCL4), ARE
ELEVATED IN PATIENTS WITH ANTIPHOSPHOLIPID
SYNDROME (APS)
Sikara M., Patsouras M., Tzioufas A. and Vlachoyiannopoulos P.
Dept of Pathophysiology, School of Medicine, National University of
Athens, Athens, Greece
Background: Platelet derived chemokines, such as PF-4 and a recently
isolated protein product of its nonallelic variant gene PF-4var, are
implicated in several aspects of vascular thrombosis and inflammation.
The above chemokines present only 4.3% aminoacid divergence in the
mature proteins; however they exhibit distinct platelet secretion mode
and function. The precise role of PF-4var regarding the haemostatic
balance is not yet studied.
Previous study from our group demonstrates a novel interaction
between b2-glycoprotein I (b2GPI), the major autoantigen in APS,
and PF-4 or PF-4var. This complex formation leads in the stabilization
of b2GPI dimeric structure which facilitates the antibody recognition
and platelet activation, as indicated by p38MAPK phosphorylation
and thromboxane production.
Objectives: To determine PF-4var plasma levels and platelet PF-4var
expression (RNA level) in patients with APS and evaluate the correlation with clinical and laboratory parameters of the disease.
Methods: From 90 patients, who fulfill the revised diagnostic criteria
for APS, blood samples were taken and separate samples of serum,
plasma and platelets were isolated. Complete blood count, C-reactive
protein (CRP), erythrocyte sedimentation rate (ESR), aPTT, anticardiolipin (anti-CL) and anti-b2GPI antibodies were measured.
(6%)
(8%)
(6%)
(8%)
(20%)
(20%)
(14%)
(12%)
(12%)
(26%)
(86%)
(40%)
(38%)
(94%)
(74%)
(6%)
(32%)
(26%)
(30%)
(18%)
(14%)
(8%)
(8%)
(36%)
(36%)
(23%)
(4%)
(41%)
(54%)
(18%)
(41%)
(45%)
(31%)
(86%)
(54%)
(59%)
(95%)
(90%)
(9%)
(54%)
(27%)
(40%)
(50%)
(50%)
(27%)
(4%)
A healthy control (n55) and a disease control group (SLE, n30)

were included in the study.
Plasma levels of PF-4var were determined using a commercially available ELISA, which absolutely discriminates PF-4var from PF-4 protein. Statistical analyses were evaluated by Mann-Whitney t-test and
Kruskal-Wallis test.
Platelet PF-4var and PF4 RNA levels were determined in RNA isolated from donors and patients platelet preparations using quantitative Real-Time PCR.
Results: APS patients showed higher levels of plasma PF-4var compared to healthy individuals or SLE patients (APS: median 137.4 pg/
ml; intarquartile range 65.69-219.2 pg/ml versus HD: 60.52 [36.0497.12] pg/ml, p<0.0001 or SLE: 51.20[16.37-172.9] pg/ml,
p0.0027). In addition, RT-PCR revealed significantly higher PF4var expression in platelets derived from APS patients comparing to
healthy donors or lupus patients(2-CT: APS: 1.461; [0.6743-2.796]
versus HD: 0.815 [0.4260-1.132], p0.0020 or SLE: 0.7505 [0.47901.136] p0.0017). PF-4var levels were significantly elevated in patients
suffering from primary APS (PAPS) than those with APS secondary to
SLE (SAPS) [p0.0086]. Regarding the clinical presentation of the
disease, patients who experienced thrombotic events versus pregnancy
morbidity or arterial versus venous thrombotic events do not show
statistically significant difference in PF-4var levels. A positive correlation was also revealed between the presence of thrombocytopenia and
the elongation of aPTT with the higher PF-4var levels (p 0.0048 and
p0.0195, respectively).
Conclusions: Preliminary results suggest that higher PF-4var levels are
present in plasma of APS patients and especially in those with PAPS
and these are associated with laboratory characteristics indicative for
higher risk
Lupus
482
A083
RARE AUTOANTIBODIES TO CELLULAR ANTIGENS IN
SYSTEMIC LUPUS ERYTHEMATOSUS
Fredi M.1, Cavazzana I.2, Taraborelli M.1, Cartella S.2, Tincani A.1 and
Franceschini F.2
1
Spedali Civili and University of Brescia,Rheumatology and Clinical
Immunology, Brescia, Italy 2Spedali Civili of Brescia, Rheumatology and
Clinical Immunology, Brescia, Italy
Introduction: A high number of antinuclear antibody specificities can
be detected in Systemic Lupus Erythematosus (SLE). Some of them are
related to a distinct clinical subset of disease, independently from their
frequency.
Aim: To investigate in a cohort of SLE patients, the prevalence and the
clinical relevance of autoantibodies to cellular antigens less frequently
found in SLE in our cohort of patients
Patients and methods: Antinuclear antibodies were detected by indirect
immunofluorescence on HEp-2 cells while counterimmunoelectrophoresis was used to detect anti-ENA antibodies in 540 patients. Clinical
and serological features were collected from charts.
Results: 319(58.9%) out of 540 sera were positive for anti-ENA antibodies. Anti-Sm, anti-U1RNP and anti-Ro/SSA were the more frequent specificities in our cohort. They were found in association with
mucocutaneous and vascular features confirming previous reports(1)
and mostly of these associations persisted after multivariate analysis.
Other anti-ENA antibodies were found in 50 positive sera(15.6%).
Anti-Ki antibodies were detected in 31, anti-Ku in 8, anti-centromere
in5, isolated anti-La/SSB, anti-PCNA and anti-Topo I in 3 each and
anti-Jo-1 in 2 sera. 54% of these antibodies were detected as the single
anti-ENA specificity. At multivariate analysis anti-Ki was significantly
associated with male gender while anti-Ku with African ethnicity
(P0.017 andP<0.0001 respectively). No sign of muscular or pulmonary involvement was found in anti-Jo-1 positive patients while features
of Systemic Sclerosis were detectable in 66% of anti-Topo I.
Conclusions: antibodies to cellular antigens more rarely found in SLE
are detectable in more than 15% of patients with anti-ENA antibodies.
Most of them are found as single anti-ENA specificity. Anti-Ki and
anti-Ku are found in a subset of disease, characterized by male gender
and African origin, respectively. Clinical features of scleroderma were
found only in patients with anti-Topo I.
References:
Sherer Y, et al. Autoantibody explosion in systemic lupus erythematosus: More than 100 different antibodies found in SLE patients.
SeminArthritisRheum2004;3
criteria were investigated with NVC(Sulli A, et al). Serum samples of

SLE patients and healthy controls were collected for flow-cytometric
analysis of CD40L, tPA, MCP-1, sE-selectin, IL-8, IL-6, VEGF, sPselectin, TGF-b and VCAM(Bender MedSystems,Vienna) simultaneously with NVC. Pearson chi-square/Fischers and Mann Withney
U tests were used for statistical analysis.
Results: Disease activity was present in 10 (SLEDAI >3) and damage
was present in 6 patients (SLICC index >0). In SLE, all NVC scores
were lower, microhaemorrhage scores were similar to SSc. Irregularly
enlarged capillaries and microhaemorrhages scores were higher in SLE
with damage(1,190,5 vs 0,60,5, p0,015, 0,30,3 vs 0,050,06,
p0,041). MCP-1, tPA and VCAM levels were higher in SLE than
healthy controls (Table 1). CD40L levels were higher in SLE with
damage(7474295365 vs 170918933 pg/ml, p0,020) and lower in
SLE with high serological item in SLEDAI(n7, 124766756 vs
1143931299 pg/ml, p0,017). tPA levels were higher in SLE with
high vasculitis item in SLEDAI(n5, 80917050 vs 27821507 pg/
ml, p0,032). VCAM levels were lower in patients with capillary
number score0,7 and microangiopathy evolution score0,7 (n6,
3079947 vs 46571198, p0,009 and n8, 3141823 vs 48781144
pg/ml, p0,002).
Conclusion: The frequency of NVC abnormalities were lower in SLE
except microhaemorrhages Irregular capillary enlargement, microhaemorrhages and increased CD40L were found to be related to damage.
CD40L and tPA levels were associated with serological and vasculitis
items in SLEDAI. VCAM levels were lower in late NVC findings like
capillary loss and high microangiopathic score. NVC is a promising
tool for the investigation of vascular pathology in SLE and requires
further investigation.
Table 1. Comparison of Vascular Biomarkers between SLE patients with
Raynauds and Healthy Controls
CD40L(pg/ml)
tPA(pg/ml)
MCP-1(pg/ml)
VCAM(pg/ml)
Healthy Controls (n21)
SLE (n20)
2462013051
24151279
907300
32311435
3438656415
44274089
1284523
41841330
NS
p0,02
p0,018
p0,016
NS; not significant
Treatment and management of co-morbidities

A085
A084
SEMIQUANTITATIVE CAPILLAROSCOPY ASSESSMENT AND
BIOMARKERS IN SYSTEMIC LUPUS ERYTHEMATOSUS
PATIENTS WITH RAYNAUDS PHENOMENON: A
COMPARATIVE STUDY WITH SYSTEMIC SCLEROSIS
Yalcnkaya Y.1, Cinar S.2, Artm-Esen B.1, Kamali S.1, Ocal L.1,
Deniz G.2 and Inanc M.1
1
Division of Rheumatology, Department of Internal Medicine, Istanbul
Medical Faculty, Istanbul University, Istanbul, Turkey 2DETAE,
Istanbul University, Istanbul,Turkey
Aim: We evaluate the relationship between semiquantitative scoring of
nailfold videocapillaroscopy (NVC) and biomarkers in systemic lupus
erythematosus (SLE) patients with Raynauds phenomenon(RP) and
compared to systemic sclerosis(SSc) patients to investigate the pathogenesis of microvascular abnormalities.
Patients and Metods: 20 SLE patients with RP fulfilling ACR and 72
SSc controls(49 limitted, 23 diffuse SSc) fulfilling Leroy&Medsgers
CLINICAL DETERMINANTS OF MYOCARDIAL DIASTOLIC

DYSFUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS
Pamfil C.1, Gusetu G.1, Flestea A.2, Candrea E.1, Zdrenghea M.1,
Zdrenghea D.1 and Rednic S.1
1
Iuliu Hatieganu University, Cluj, Romania 2Babes-Bolyai University,
Cluj, Romania
Introduction: Myocardial involvement is frequent, but often silent in
systemic lupus erythematosus (SLE); echocardiography is a non-invasive imaging diagnostic method that effectively detects myocardial
performance.
Aim: To determine the frequency of diastolic dysfunction and assess its
association with disease characteristics, standard cardiovascular risk
factors and damage accrual in SLE patients.
Patients and methods: Fifty-seven consecutive SLE patients underwent
standard transthoracic echocardiography (chamber diameters, LVEF,
valve abnormalities, LV diastolic performance by mitral flow
Lupus
483
assessment and TDI of the mitral ring). Demographic data, cumulative
clinical features, disease activity and damage scores were obtained.
Results: Within the cohort, 71% were female; mean standard deviation age at SLE diagnosis and disease duration were 36 11.2 years
and 9.6 8.9 years, respectively. Major/severe organ involvement
within the cohort was as follows: cardiac 40%, renal 20%, neuropsychiatric 21%, cardiac 40%, and hematologic 10%. Diastolic dysfunction was recorded in 37% of subjects and was associated with
older age (p0.019) and cumulative damage accrual (p0.04).
Among types of symptomatic cardiac involvement, diastolic dysfunction was associated with endocarditis (p0.05). The presence of other
severe disease manifestations or associated autoimmune diseases did
not impact the diastolic dysfunction. Diastolic dysfunction was associated with the presence of antiphospholipid antibodies (p0.037),
with anticardiolipin antibodies (p0.05), but not with SLE-related
autoantibodies. Furthermore, diastolic dysfunction was associated
with antiphospholipid syndrome (p0.05) and a history of cardiovascular events, in particular deep vein thrombosis (p0.03). Importantly,
at least one cardiovascular risk factor was present in 40% of subjects
but did not influence the development of diastolic dysfunction. A history of prolonged antiaggregant or anticoagulant therapy did not incur
a protective effect against diastolic dysfunction.
Conclusions: Myocardial diastolic dysfunction is a frequent echocardiographic finding. Cumulative organ damage and antiphospholipid
antibodies, but not cardiovascular risk factors, are major determinants
for diastolic dysfunction in SLE patients.
References
1 Paran D, et al. Ann Rheum Dis. 2007;66(4):506510..
A086
CLINICAL IMPACT OF REPEAT RENAL BIOPSIES IN
PATIENTS WITH LUPUS NEPHRITIS
Marinaki S.1, Kapsia H.1, Liapis G.2, Nakopoulou L.2, Skalioti C.1,
Sinodinou I.1 and Boletis J.N.1
1
Nephrology Department and Renal Transplantation Unit, Laiko
Hospital, Athens, Greece 2Pathology Department, Medical School,
University of Athens
Introduction: The clinical impact of repeat renal biopsies in patients
with S.L.E. is still debatable.
Aim: This retrospective analysis aimed to assess the hypothesis that
repeat biopsy is essential for determining the activity and chronicity
status of the disease and is a reliable tool in guiding therapeutic
decisions.
Patients and Methods: We retrospectively analyzed laboratory parameters and therapeutic changes in 20 patients with lupus nephritis and
repeat renal biopsies. Biopsies were blindly reassessed by two renal
pathologists and were compared according to the newest ISN/RPS
classification.
Results: Twenty SLE patients had two renal biopsies, 8 had three, 5
had four, 4 had five and 1 patient had six. Median time between first
and second, second and third, third and fourth, fourth and fifth biopsy
was 28, 35, 33 and 28 months respectively. Mean activity index from
the first to the fifth biopsy was 7.9, 5.2, 7, 9.4, 4.7 while mean chronicity index was 1.9, 2, 4.3, 5.2, 7.7 respectively. Histological conversion
was observed in 58% of repeat biopsies, the most frequent being
between classes III and IV (21%). In 10.5% there was conversion
from proliferative to non proliferative class. In 2.6% there was the
exact opposite transition. In 5.2% there were no findings of S.L.E.
nephritis. In 21% there was a transition to a more severe form of
nephritis. There was no correlation between laboratory parameters
and the type of conversion. In 84% there was a change in therapeutical
strategy after the repeat biopsy, either in means of increase (76%) or

decrease (8%) of immunosuppression.
Conclusion: Repeat biopsy is a reliable tool for monitoring the activity
and chronicity status of the disease and for guiding therapeutic decisions especially late in the course of the disease.
References
1 Daleboudt GMN, et al. The clinical relevance of a repeat biopsy in
lupus nephritis flares. Nephrol Dial Transplant 2009; 24:
37123717..
2 Lu J, et al. Repeat renal biopsy in lupus nephritis: a change in
histological pattern is common. Am J Nephrol 2011; 34: 220225.
3 Wang G et al. Changes in pathological pattern and treatment regimens based on repeat renal biopsy in lupus nephritis. Chinese
Medical Journal 2012(125);16:2890-2894.
4 Moroni G , et al. Clinical and prognostic value of serial renal
biopsies in lupus nephritis. Am J K idney Dis 1999; 34: 530539.
5 Abdulkareem A, et al. Strategy for second kidney biopsy in patients
with lupus nephritis. Nephrol Dial Transplant 2011; 0: 17.
A087
LOW-MEDIUM DOSE PREDNISONE TO TREAT MODERATESEVERE LUPUS ACTIVITY: SAME EFFICACY, LESS
TOXICITY
Barbosa C., Ruiz Arruza I., Ugarte A. and Ruiz Irastorza G.
Autoimmune diseases research unit. Hospital Universitario Cruces.
UPV/EHU
Objective: To analyse the efficacy and toxicity of low-medium prednisone-based regimes to treat moderate-severe lupus activity.
Methods: We selected from the Lupus-Cruces longitudinal cohort 41
patients presenting at the time of the diagnosis of SLE with moderatesevere lupus activity, defined as a SLEDAI score 6, and who were
treated using different regimes combining medium-low dose prednisone (i.e. 30 mg/d) with hydroxychloroquine, pulse-methyl prednisolone and/or immunosuppressive drugs. These patients were matched
according to their SLEDAI score with 41 historic controls who
received high doses of prednisone at SLE diagnosis. In order to compare the efficacy of both schemes, the evolution of the SLEDAI scores
at year 2 was compared. In order to analyse toxicity, damage at year 5,
as measured by the SLICC damage index (SDI), and glucocorticoidattributed damage (defined as new diabetes mellitus, osteoporotic fractures, osteonecrosis and/or cataracts) were compared between both
groups.
Results: There were no differences between both groups regarding
gender distribution, autoantibody profile and baseline SDI. Likewise,
baseline SLEDAI was similar in both groups (10 vs. 10.9, respectively,
p0.31). Patients in the low-dose group were older at SLE diagnosis
(38 vs. 31 years, respectively, p0.035), whilst proliferative lupus nephritis was more frequent among patients in the high-dose group (12%
vs. 32%, respectively, p0.06). The mean maximum prednisone dose
received was significantly lower in the low-dose group (11 vs. 63 mg/d,
respectively, p<0.001) as well as the average daily prednisone dose
received during the first year (4.5 vs. 24 mg/d, respectively,
p<0.001). The use of antimalarials and pulse methyl-prednisolone
was more frequent among patients in the low-dose group (100% vs.
27%, p<0.001; 34% vs. 12%, p0.035), whilst there were no differences in the use of immunosuppressive drugs (34% vs. 46%, p0.36).
The mean SLEDAI at year 2 and the mean reduction in SLEDAI
between baseline and year 2 were similar in both groups (4.4 vs. 5.2,
p0.4; 5.5 vs. 5.7, p0.8). On the contrary, patients in the low-dose
group had a lower SDI score at year 5 (0.4 vs. 1, p0.01) and a lower
increase of the SDI score from baseline (0.31 vs. 0.87, p0.004).
Likewise, the frequency of prednisone-attributed damage at year 5
was lower in patients in the low-dose group (2% vs. 22%, p0.01).
Lupus
484
Conclusion: The use of therapeutic regimes containing low-medium
doses of prednisone, combined with hydroxychloroquine, pulsemethyl prednisolone and/or immunosuppressive drugs, is as effective
and has less associated toxicity than high dose prednisone-b
A088
TREATMENT AND RENAL OUTCOME OF RAPIDLY
PROGRESSIVE GLOMERULONEPHRITIS IN LUPUS
PATIENTS
Marinaki S.1, Kapsia H.1, Gakiopoulou X.2, Liapis G.2, Skalioti C.1 and
Boletis J.N.1
1
Nephrology Department and Renal Transplantation Unit, Laiko
Hospital, Athens, Greece, 2Pathology Department, Medical School,
University of Athens, Greece
Introduction: Proliferative lupus nephritis (LN) has a worse outcome
and while crescents are common, rapidly progressive glomerulonephritis (RPGN) is rather rare and not clearly distinguished from the
proliferative classes. In two large series of lupus patients from Far
East the incidence of RPGN in LN is 3.5%. Therefore, data regarding
the therapy and clinical outcome of RPGN in lupus patients is scarce.
Aim: Evaluation of treatment and renal outcome of RPGN in lupus
patients with the use of repeat renal histology.
Patients and Methods: In a series of 195 renal biopsies performed in
lupus patients during 2000-2013, RPGN was observed in 5 (2.5%).
Table 1. Histological findings at initial biopsy
Tubular
SLE Activity Chronicity
Atrophy/Interstitial Glomerulosclerosis
Class Index Index
Crescents (%) Fibrosis (%)
(%)
1 IV
20
2 IV
17
3 IVV 14
4 IV
14
5 IV
21
4
6
5
6
0
77
70
50
53
53
10
35
10
40
10
Three of them were men and 2 women, aged 21 to 54 years, with

proliferative LN (III or IV) and >50% crescent formation in the initial
biopsy. All patients were treated with 3 daily i.v. pulses of methylprednisolone (0.5-1g/24h) and 6 monthly i.v. pulses of cyclophosphamide
(0.5-1g/m2) in combination with the anti-CD20 monoclonal antibody
Rituximab (1g/2weeks). Immunoadsorption sessions (6-8) were also
applied. A protocol renal biopsy was performed in a median time of
19.6 months from the initial biopsy.
Results: Histology and laboratory parameters are presented in Tables
1-3 and were examined from the time of initial biopsy until the end of
follow-up (12/2013).
All protocol biopsies revealed a substantial increase in chronic lesions,
especially glomerulosclerosis while 2 patients developed secondary
FSGS. However, e GFR had a tremendous improvement in all but
one patient (No 4), who had the most severe chronic lesions already
at the time of initial biopsy.
Conclusions: The frequency of RPGN in lupus patients is low.
Intensive therapy leads to rapid and long-standing improvement of
renal function although it does not prevent the progression of histological chronic lesions.
References
1 Sumethku V, et al. Lupus nephritis: a challenging cause of rapidly
progressive crescentic glomerulonephritis. Lupus 2009; 9: 424428.
2 Blake JS, et al. Rapidly progressive lupus glomerulonephritis and
concomitant microangiopathy in an adolescent. Lupus 2002;
11(85335.
3 Tang Z, et al. Clinical spectrum of diffuse crescentic glomerulonephritis in Chinese patients. Chin Med J(Engl) 2003;
116(1117311740.
4 Chen S, et al. Significance of histological crescent formation in
patients with diffuse proliferative lupus nephritis. Am J Nephrol
2013; 38(644552.
5
11
15
25
12
Table 2. Histological findings at protocol biopsy
1
2
3
4
5
Time from initial

biopsy (months)
SLE
class
Activity
Index
Chronicity
Index
Other Histological
Findings
Tubular
Atrophy/Interstitial
Fibrosis (%)
Glomerulo-sclerosis
(%)
12
19
22
24
21
III
III
-
3
0
-
8
5
-
FSGS
FSGS
25
35
10
50
10
48
45
21
58
21
Table 3. Renal function and proteinuria during follow-up time

At 6th month
At initial Biopsy
At time of Protocol Biopsy
At end of follow-up
eGFR (ml/min) Proteinuria (g/24h) eGFR (ml/min) Proteinuria (g/24h) eGFR (ml/min) Proteinuria (g/24h) eGFR (ml/min) Proteinuria (g/24h)
1
2
3
4
5
33
38
39
22
26
3
7.8
5.3
3
6
96
83
87
33
97
8.5
3
2.6
2.8
0.9
111
104
95
27
111
10
1
0.15
1.8
0.8
Lupus
92
81
94
28
131
0.15
0.92
1
4
0.3
485
New therapies, novel targets of therapy and regulatory issues

A089
AUTOREACTIVE LONG-LIVED PLASMA CELLS IN NZB/W
MICE AND THEIR REGENERATION
Taddeo A.1,2, Khodadadi R.1, Cheng Q.1,2, Manz R.A.3, Radbruch A.2,
Hiepe F.1,2 and Hoyer B.F.1,2
1
Department of Rheumatology and Clinical Immunology, Charite
University Hospital Berlin, Berlin, Germany 2German Rheumatism
Research Centre, a Leibniz Institute, Berlin, Germany 3Institute for
Systemic Inflammation Research, University of Luebeck, Luebeck,
Germany
Introduction: Autoantibodies contribute significantly to the pathogenesis of systemic lupus erythematosus (SLE) [1]. The long-lived plasma
cells (LLPC) secreting such autoantibodies are refractory to conventional immunosuppressive treatments [2, 3]. Although they are generated long before the disease becomes clinically apparent, it is unknown
whether their generation continues in the established disease.
Aim: Here, we analyze the generation of autoreactive LLPCs in lupusprone NZB/W F1 mice over their lifetime, and LLPC regeneration
after depletion.
Material and methods: Bromodesoxyuridine pulse chase experiments
were used to analyse the kinetic of the development of the LLPC compartment in lupus-prone NZB/W F1 mice. Depletion was performed
using bortezomib and cyclophsphamide. LLPC were anylsed using
flow cytometry and ELIspot technique.
Results: Autoreactive LLPCs are established in the spleen and bone
marrow of lupus-prone mice very early in ontogeny, before week 8 and
before the onset of symptoms. The generation of LLPCs then continues throughout life. LLPC counts in the spleen plateaued by week
10, but continued to increase in the bone marrow. When LLPCs are
depleted by the proteasome inhibitor bortezomib, their numbers regenerate within two weeks. Persistent depletion of LLPCs was achieved
only by combining a shot of bortezomib with maintenance therapy,
e.g., cyclophosphamide, depleting the precursors of LLPCs or preventing their differentiation into LLPCs.
Conclusion: In lupus-prone NZB/W F1 mice, autoreactive LLPCs are
generated throughout life. Their sustained therapeutic elimination
requires both the depletion of LLPCs and the inhibition of their
regeneration.
References
1 Hiepe F, Dorner T, Hauser AE, Hoyer BF, Mei H, Radbruch A .
Long-lived autoreactive plasma cells drive persistent autoimmune
inflammation. Nature reviews Rheumatology 2011 Mar;
7(3170178.
2 Hoyer BF, Moser K, Hauser AE, Peddinghaus A, Voigt C, Eilat
D, et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. The
Journal of experimental medicine 2004 Jun 7; 199(1115771584.
3 Mumtaz IM, Hoyer BF, Panne D, Moser K, Winter O, Cheng Q,
et al. Bone marrow of NZB/W mice is the major site for plasma cells
resistant to dexamethasone and cyclophosphamide. Journal of
Autoimmunity 2012 Sep; 39(3180188.
A090
DECREASED SLE DISEASE ACTIVITY AND
CORTICOSTEROID USAGE AND NO RENAL FLARES DURING
BELIMUMAB TREATMENT
Parodis I.1, Svenungsson E.1, Axelsson M.2 and Gunnarsson I.1
1
Department of Medicine, Rheumatology Unit, Karolinska Institutet,
Stockholm, Sweden 2AlbaNova, Stockholm University, Stockholm,
Sweden
Introduction: Belimumab is a recombinant monoclonal antibody that
specifically binds to soluble B-lymphocyte stimulator, thereby reducing
autoantibody levels. It is the only biologic agent approved for treatment of Systemic Lupus Erythematosus (SLE).
Aim: To investigate the effects of belimumab given as an add-on to
patients with active SLE despite standard-of-care therapy, with focus
on low-active lupus nephritis (LN) patients.
Patients and Methods: Fourteen patients were included. Clinical data
were acquired at baseline and week 12, 26 and 52. Disease activity was
assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and
Systemic Lupus Activity Measure (SLAM). The primary organ manifestations comprised arthritis (n9), skin involvement (n11), serositis
(n3), involvement of the central nervous system (n4) and cytopenias
(n3). Nine patients with former LN were included (median proteinuria at baseline 0.2 g/day, range 0.01-0.4 g/day).
Results: At baseline, all patients received oral prednisolone (mean dose
11, range 5-20 mg/day), 9 received antimalarials, 3 mycophenolate
mofetil, 2 azathioprine, and 1 cyclosporine. The median SLEDAI
and SLAM scores were 10 (range 2-24) and 12 (range 5-23), respectively. One patient withdrew due to allergic reaction.
Significant decreases of SLAM and SLEDAI were seen at week 26
(p0.001 and p0.007, respectively) and 52 (p0.028 and p0.012,
respectively). Prednisolone dosages were significantly decreased compared to baseline at week 26 (p0.003) and 52 (p0.008).
Ten patients had low complement at baseline. We observed no significant increase in C3/C4 levels. In the patients with former LN, no renal
flare was observed during the observation period. The grade of proteinuria remained unchanged at week 26 (median 0.14 g/day, range
0.01-0.5 g/day) and 52 (median 0.13 g/day, range 0.02-0.24 g/day).
No severe adverse events were noted.
Conclusions: Belimumab treatment decreased SLE disease activity and
reduced corticosteroid usage. Despite the limited number of patients,
our observations indicate that belimumab may prevent renal flares and
may be used in patients with former LN and persistent
A091
EPRATUZUMAB MAINTAINS IMPROVEMENTS IN DISEASE
ACTIVITY FOR OVER 2 YEARS IN PATIENTS WITH
MODERATE-TO-SEVERE SYSTEMIC LUPUS
ERYTHEMATOSUS
Clowse M.E.B.1, Houssiau F.2, Petri M.3, Kilgallen B.4, Kalunian K.5,
Strand V.6, Bongardt S.7, Gordon C.8 and Wallace D.J.9
1
Duke University Medical Center, Durham, USA 2Universite Catholique
de Louvain, Brussels, Belgium 3School of Medicine, Johns Hopkins
University, Baltimore, USA 4UCB Pharma, Raleigh, USA 5UCSD
School of Medicine, La Jolla, USA 6Biopharmaceutical Consultant;
Portola Valley, USA 7UCB Pharma, Brussels, Belgium 8University of
Birmingham, Birmingham, UK 9Cedars-Sinai Medical Center, Los
Angeles, USA
Introduction: In the EMBLEMTM 12-week dose-ranging phase IIb
study, epratuzumab (a monoclonal antibody targeting CD22) produced clinically relevant improvements in disease activity in patients
with moderate-to-severe systemic lupus erythematosus (SLE).
Lupus
486
Table 1. Combined treatment response, BILAG, SLEDAI,and PGA scores from EMBLEMTM baseline through to Wk 108 and last visit
All patients
Combined Treatment Response (%)
EMBLEMTM
placebo patients (%)
EMBLEMTM
epratuzumab patients (%)
BILAG median (range)
SLEDAI median (range)
PGA median (range)
EM
BLEMTM baseline
OLE
screening
Week 48
Week 96
Week 108
Last Visita
32.5
25.7
40.7
38.2
57.2
58.6
56.5
62.5
60.3
57.1
41.6
45.7
33.9
41.3
56.9
55.0
61.1
40.7
25.0 (1261)
12.0 (639)
50.0 (990)
14.0 (057)
10.0 (034)
31.0 (096)
9.0 (052)
6.0 (030)
18.0 (081)
9.0 (052)
5.0 (022)
19.0 (073)
9.0 (052)
4.0 (024)
17.5 (069)
10.0 (072)
8.0 (032)
25.0 (094)
Last visit last available value for each subject regardless of timing
Aim: To report long-term efficacy of epratuzumab from the open-label

extension (OLE) (SL0008) of EMBLEMTM (NCT00660881).
Patients and Methods: EMBLEMTM patients who completed 12 weeks
blinded treatment or discontinued after 8 weeks due to lack of efficacy were eligible for the OLE, receiving 1200mg epratuzumab at
Weeks 0 and 2 of 12-week cycles with efficacy evaluated at Weeks 4
and 8. Endpoints included BILAG improvement, SLEDAI assessment
score, Physician Global Assessment (PGA) score and combined treatment response (BILAG improvement without worsening, no SLEDAI
worsening, no PGA worsening relative to baseline). Observed data are
reported to OLE Week 108.
Results: In the OLE, median (range) epratuzumab exposure was 845
(751185) days across 203 patients; 35 (17%) and 168 (83%) received
placebo and epratuzumab (various doses) respectively in
EMBLEMTM. Consistent BILAG, SLEDAI and PGA improvements
were observed between EMBLEMTM baseline and OLE Week 108
(Table 1). Median BILAG total score decreased by 64%. At Week
108, 94.0% and 97.4% had no worsening in SLEDAI and PGA
respectively, and 60.3% met combined treatment response criteria
(Table 1). Improvements from BILAG A/B to BILAG C or D were
observed across body systems (44.8%, 41.6%, 34.7%, 36.0%, 84.1%
and 52.0% in the musculoskeletal, mucocutaneous, cardiorespiratory,
neuropsychiatric, constitutional and renal body systems respectively).
Conclusion: Epratuzumab was associated with sustained improvements, beyond 2 years, in disease activity in patients with moderateto-severe SLE.
Aim: To evaluate the long-term safety profile and effect on corticosteroid (CS) use of epratuzumab treatment in patients with moderate-tosevere SLE.
Patients and Methods: EMBLEMTM patients who completed 12 weeks
blinded treatment or discontinued after 8 weeks due to lack of efficacy were eligible for entry into an open-label extension (OLE) study,
receiving 1200mg epratuzumab at Weeks 0 and 2 of 12-week cycles
with efficacy evaluated at Weeks 4 and 8. Safety variables included
exposure duration, adverse events (AEs), infusion reactions/infections.
CS doses were converted to prednisone equivalents. Data are summarized using descriptive statistics.
Results: 203 patients received a median 845 (range:751185) days epratuzumab exposure. Median CS dose was 10.0mg/day at EMBLEMTM
baseline and OLE entry, and 5.0mg/day at Week 116
(n112).Proportion of patients requiring CS 7.520mg/day and
>20mg/day decreased (49.8% and 10.8% at OLE entry, 33.9% and
8.0% at Week 116, respectively). AEs are summarized in the Table 1.
There were no opportunistic infections, no patterns of specific serious
(n14 [6.9%]) infections, and no indication of an increased risk of
malignancies. One patient died of cardiac failure.
Conclusions: Long-term treatment with epratuzumab was associated
with decreases in CS use in those receiving >7.5mg/day.
Epratuzumab had an acceptable safety profile, with no new safety
signals identified.
Table 1.
Category
Patients, n
Patients, %
Events, n
Any AE
Related to study drug
Causing discontinuation
Serious AEs
SLE flare
Lupus nephritis
Symptomatic cholelithiasis
Infections/infestations
Urinary tract infection
Upper respiratory tract infection
Sinusitis
Infusion reactions
Deaths
192
87
29
57
7
4
3
138
50
47
22
29
1
94.6
42.9
14.3
28.1
3.4
2.0
1.5
68.0
24.6
23.2
10.8
14.3
0.5
1946
300
35
98
7
4
3
487
87
93
30
74
1
A092
EPRATUZUMAB: SUSTAINED LONG-TERM SAFETY
PROFILE AND EFFECT ON CORTICOSTEROID USE IN
PATIENTS WITH MODERATE-TO-SEVERE SYSTEMIC LUPUS
ERYTHEMATOSUS
Wallace D.J.1, Ordi-Ros J.2, Neuwelt M.3, Kalunian K.4, Kilgallen B.5,
Bongardt S.6, Petri M.7, Pike M.8, Jeka S.9, Gordon C.10 and
Strand V.11
1
Cedars-Sinai Medical Center, Los Angeles, USA 2Hospital Vall
dHebron, Barcelona, Spain 3East Bay Rheumatology Medical Group,
San Leandro, USA 4UCSD School of Medicine, La Jolla, USA 5UCB
Pharma, Raleigh, USA 6UCB Pharma, Brussels, Belgium 7School of
Medicine, Johns Hopkins University, Baltimore, USA 8Harvard Medical
School, Harvard, USA; University Hospital No. 2, Bydgoszcz, Poland
10
University of Birmingham, Birmingham, UK 11Biopharmaceutical
Consultant, Portola Valley, USA
Introduction: In the EMBLEMTM 12-week dose-ranging phase IIb
study, epratuzumab (a monoclonal antibody targeting CD22) was
safe and effective in the treatment of patients with moderate-tosevere systemic lupus erythematosus (SLE).
Lupus
487
A093
IMMUNOLOGIC RESPONSE TO EPRATUZUMAB IN

PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Petri M.1, Gordon C.2, Kalunian K.3, Pike M.4, Houssiau F.5,
Strand V.6, Leszczynski P.7,8, Keiserman M.9, Wegener W.A.10,
Wallace D.J.11, Bongardt S.12, Kilgallen B.13 and Goldenberg D.M.10,14
1
The Johns Hopkins University, Baltimore, USA; 2University of
Birmingham, Birmingham, UK; 3University of California, San Diego,
USA; 4Harvard Medical School, Boston, USA; 5Universite Catholique
de Louvain, Belgium; 6Biopharmaceutical Consultant, Portola Valley,
USA; 7Poznan Medical University; 8Jozef Strus Municipal Hospital,
Poznan, Poland; 9Hospital San Lucas Da Pucrs, Porto Alegre, Brazil;
10
Immunomedics Inc, Morris Plains, USA; 11Cedars-Sinai Medical
Center, Los Angeles, USA; 12UCB Pharma, Belgium, Brussels; 13UCB
Pharma, Raleigh, USA; 14Center for Molecular Medicine and
Immunology, Morris Plains, USA
Introduction: Epratuzumab (a monoclonal antibody targeting CD22),
produced clinically-relevant improvements in disease activity in moderate-to-severe systemic lupus erythematosus (SLE) patients in the
EMBLEMTM study.
Aim: To report immunologic response in short-term and long-term
epratuzumab trials.
Patients and Methods: In the ALLEVIATE-1/2 trials, patients received

placebo, 360mg/m2 or 720mg/m2 epratuzumab in 12-week cycles up to
48 weeks; the SL0006 open-label extension (OLE) utilized 360mg/m2
epratuzumab. In EMBLEMTM, patients received 12 weeks placebo or
epratuzumab (dose-ranging up to 3600mg cumulative dose); patients
entering the OLE (SL0008) received 1200mg epratuzumab at Weeks 0
and 2 of repeating 12-week cycles. Peripheral blood CD19 B-cell
counts, B-cell surface CD22, CD3 T-cell counts and IgG/IgA/IgM
levels were measured.
Results: After 12 weeks epratuzumab treatment, B-cell counts were
reduced from baseline in ALLEVIATE and EMBLEMTM (Table 1).
Decreases continued into OLEs, stabilising between -50% and -65% at
most timepoints from Week 72. CD22 expression rapidly decreased
(around 80% of baseline by Week 4); this decrease was maintained
throughout SL0008. In SL0008, CD27-/IgD-/CD95 B cells (a
memory B-cell subset elevated in SLE flares) were also reduced. Tcell counts remained stable (2 years in SL0008; 4 years in SL0006).
Median IgM levels decreased (SL0006 year 1 29% of baseline;30%
to 40% at most timepoints thereafter), median IgA/IgG levels
decreased minimally from baseline.
Conclusions: B-cell counts were moderately reduced after 12 weeks
epratuzumab treatment. Long-term treatment was associated with profound decreases in B-cell CD22.
Table 1. Median (range) absolute B-cell counts (cells/mL) and median percent (range) change from baseline in B-cell counts during short and long-term SLE
treatment with epratuzumab
Median (range) absolute B-cell counts (cells/mL)
EMBLEMTM
ALLEVIATE
360 mg/m2
720 mg/m2
All active
Placebo
600 mg weekly 100 mg EOW 400 mg EOW 1200 mg EOW 1800 mg EOW Placebo
Baseline
99.5 (101814) 134.0 (101529) 104.0 (101814) 53.0 (10946) 125.0 (61002) 140.0 (10818) 149.5 (19931) 94.0 (9727)
116.0 (111122) 142.5 (3508)
40
11
51
37
37
Week 12
59.0 (10659)
60.5 (27362)
60.5 (10659)
86.0 (101291) 109.0 (1615) 100.5 (14558) 91.0 (17533) 94.5 (13415) 80.0 (18465)
34
39
34
37
36
111.0 (16474)
% change (range)* -34.1 (-92145) -55.1 (-75220) -36.9 (-92220) 1.9 (-86770) -19.3 (-9985) -15.2 (-75126) -28.9 (-7540) -14.3 (-75122) -26.6 (-7973)
-14.6 (-581767)
29
34
10
44
30
28
SL0006 360 mg/m2
32
26
Screening V1
41.0 (201303)
Screening V1 95.0 (1615)
% (range)*
37.7 (89357)
% (range)*
17.2 (991767)
25
195
Week 48
56.5 (20586)
Week 48
70.0 (0526)
% (range)*
45.7 (88313)*
% (range)
46.0 (100215)
28
142
Week 96
63.5 (20394)
Week 96
60.0 (6379)
% (range)*
51.1 (81219)
% (range)*
49.4 (97244)
22
111
Week 144
51.0 (20460)
Week 112
59.0 (3274)
% (range)*
48.0 (93325)
% (range)*
50.0 (94286)
21
106
Week 192
48.5 (20449)
% (range)*
66.6 (84462)
18
32
33
SL0008 1200 mg
* Median (range) percent change in B-cell counts from baseline
Lupus
488
A094
A095
A PHASE 2 TRIAL OF ALLOGENEIC HUMAN UMBILICAL

CORD DERIVED MESENCHYMAL STEM CELL FOR THE
TREATMENT OF LUPUS NEPHRITIS (CTS.GOV IDENTIFIER:
NCT 01539902)
Deng D.1, Zhang P.1, Guo Y.1, Tseu F.L.2 and Lim T.O.3
1
Department of Dermatology 2nd Affiliated Hospital of Kunming
Medical University, SLE Research Centre Yunnan China 2Sabah
Medical Centre Sabah Malaysia 3ClinResearch SB Malaysia
SUSTAINED IMPROVEMENTS IN HEALTH-RELATED

QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC LUPUS
ERYTHEMATOSUS FOLLOWING EPRATUZUMAB
TREATMENT: RESULTS FROM A PHASE IIB TRIAL AND ITS
OPEN-LABEL EXTENSION
Strand V.1, Merrill J.T.2, Nika E.3, Kilgallen B.3, Regnault A.4 and
Gordon C.5
1
Biopharmaceutical Consultant, Portola Valley,USA; 2Oklahoma
Medical Research Foundation, Oklahoma, USA; 3UCB Pharma,
Raleigh,USA; 4Mapi HEOR & Strategic Market Access, Lyon, France;
5
University of Birmingham, Birmingham, UK.
Background and Aims: The aim of the study was to evaluate the efficacy of allogeneic Human Umbilical Cord derived Mesenchymal Stem
Cell (hUC-MSC) for the treatment of proliferative lupus nephritis. The
study was motivated by previous reports that showed dramatic
response to hUC-MSC in patients with severe refractory SLE.
Methods: Eighteen patients with WHO Class IV lupus nephritis were
randomly assigned to either hUC-MSC (dose 2X108 cells) or placebo.
All patients received standard immunosuppressive treatment which
consisted of intravenous methylprednisolone and cyclophosphamide
as induction, followed by maintenance oral prednisolone and mycophenolate mofetil. This Phase 2 trial was based on Simons optimal
two-stage design which requires 12 patients be enrolled in the first stage
and an additional 24 patients in the second stage if >7 patients were
to respond to hUC-MSC in the first stage (and the response rate were
to exceed that of the parallel placebo control group).
Results: Remission occurred in 9 of 12 patients (75%) in the hUCMSC group and 5 of 6 patients (83%) in the placebo group.
Remission was defined as stabilization in renal function, <10 urinary
RBC/hpf and >50% reduction in proteinuria or <1g/day for subnephrotic proteinuria or to <3g/day for nephrotic range proteinuria
at baseline. 17% of patients in both the hUC-MSC and placebo group
achieved complete remission. Improvements in serum albumin, serum
complement, ANA, anti-dsDNA, proteinuria, urinary activity, renal
function, SLEDAI and BILAG score were similar in both groups.
One patient on placebo had a stroke and another had ascites of
unknown cause. One patient on hUC MSC had leucopenia, pneumonia and subcutaneous abscess from which she recovered. Another had
severe pneumonia which she died of.
Conclusion: hUC-MSC has no apparent additional effect over and
above standard immunosuppression.
Introduction: Improvements in health-related quality of life (HRQoL)

with epratuzumab (a monoclonal antibody targeting CD22) in systemic lupus erythematosus (SLE) patients have been reported in the
ALLEVIATE trials from Week (Wk)12 and sustained to 4 years. In the
EMBLEMTM study (dose-ranging phase IIb randomized controlled
trial [RCT] in SLE), epratuzumab treatment resulted in clinically relevant improvements in disease activity.
Aim: To report HRQoL data from EMBLEMTM and its open-label
extension (OLE) (NCT00660881).
Methods: In EMBLEMTM, patients with moderate-to-severely active
SLE (1 BILAG 2004 A or 2 Bs) were randomized to 1 of 6 12-week
intravenous regimens plus standard of care (SOC): placebo, or cumulative dose (cd) epratuzumab (200/ 800/2400/3600mg) as 2 equal every
other week infusions, or 2400mg cd as 600mg every week. Patients
completing 12 weeks or discontinuing due to lack of efficacy after
8 weeks were eligible for OLE entry, receiving 1200mg epratuzumab
at Wks0 and 2 of 12-week cycles. HRQoL was assessed using Short
Form-36 (SF-36) v2.0. Data are reported to the end of EMBLEMTM
and OLE Wks48 and 108. Mean changes and %pts reporting improvements minimum clinically important differences (MCID) (increases
from baseline5.0-points in domain and 2.5-points in physical and
mental component scores [PCS and MCS]) are presented. OLE
observed case analyses are presented.
Results: Mean SF-36 PCS, MCS and domain scores across all groups
generally increased from EMBLEMTM baseline through Wk12, with
greater increases in the PBO group. Clinically meaningful changes vs
EMBLEMTM baseline were observed in the OLE (Table 1).
Conclusions: No differences in improvements in HRQoL were observed
with epratuzumab and PBO in the EMBLEMTM study, potentially due
to short-term treatment, small sample sizes and background therapy.
Long-term improvements in the OLE were consistent with those in the
ALLEVIATE RCTs.
Table 1. SF36 scores and MCID with epratuzumab in EMBLEMTM and EMBLEMTM OLE
EMBLEMTM baseline
EMBLEMTM OLE screening
Week 48 of the EMBLEMTM OLE
Mean change
Mean
absolute from EMBLEMTM
Score
baseline
N
Week 108 of the EMBLEMTM OLE
Mean change
from EMBLEMTM
Mean
absolute Score baseline
N
Mean change
Mean
absolute from EMBLEMTM % pts with
Score
baseline
improvement MCID
Mean
absolute Score
Physical functioning 201
47.0
203 56.6
8.5
156 61.2
14.5
114 57.4
12.6
69.3
Role physical
201
37.9
203 51.1
13.3
156 53.5
15.1
113 54.7
16.5
73.5
Bodily pain
201
36.1
203 48.3
12.1
156 53.0
17.1
114 52.7
16.9
68.4
General health
201
32.6
203 41.3
8.7
156 46.5
13.6
114 47.8
16.2
82.5
Vitality
201
34.3
203 42.8
8.6
156 46.3
13.1
113 43.6
10.9
63.7
Social functioning
201
46.1
203 58.1
12.1
156 63.3
17.9
114 61.4
17.4
66.7
Role emotional
201
50.9
203 58.9
7.9
156 61.4
10.5
113 60.1
10.5
56.6
Mental health
201
50.8
203 57.8
7.1
156 61.5
11.6
113 60.5
11.4
66.4
PCS
201
36.1
203 38.7
4.5
156 40.1
6.4
113 40.5
67.4
70.8
MCS
201
36.1
203 40.0
3.9
156 41.6
6.0
113 40.9
5.7
59.3
SF36 domain
Lupus
489
A096
THERAPEUTIC PLASMA EXCHANGE (TPE) FOR
REFRACTORY AUTOIMMUNE DISEASES REPORT OF 60
CASES
Kiraz S., Karadag O., Soyuoz A., Kalyoncu U., Karaagac T., Kilic L.,
Helvaci O., Ozcebe O. and Ertenli I.
Hacettepe University Faculty of Medicine, Ankara Turkey
Introduction: Therapeutic Plasma Exchange (TPE) is an effective therapeutic option for treating serious manifestations of systemic autoimmune diseases.
Objective: This study is aimed to investigate the main demographic and
clinical characteristics as well as the outcome of patients with systemic
autoimmune diseases treated with TPE at an university hospital.
Material and Methods: Patients treated with TPE between 2002-2013
were included into the study. Indications for TPE, complications and
outcomes were obtained from hospital records.
Results: A total of 60 patients (Female/male: 43/17) were treated with
TPE. Mean age at the time of 41.016.5 (range: 15-73 years). Twentyone (35.0%) patients had SLE, 14 (23.4%) patients had vasculitis, 6
patients had Sjogren syndrome, 4 patients had dermato/polimyositis, 3
patients had primary antiphospholipide syndrome, 12 patients with
other diagnoses. Indications for TPE were hematologic (28.4%),
neurologic (28.3%), pulmonary (20.0%) and renal failure (23.4%),
myopathy (5.0%), hepatic (5.0%) and dermatologic (3.4%) causes.
In 9 (15%) of patients TPE had performed in case of concomitant
leucopenia or infection. Fifteen of the patients (25%) had TPE
required disease involvement as presenting feature. All patients were
receiving corticosteroids at varying doses and all received a concomitant immunosuppressive drug.
Outcome analysis had been done in 55 (91.6%) of patients. Totally 20
(33.3%) of patients died (17 of them during first treatment course, 3 of
them after discharge from hospital). More than half of the patients
with pulmonary (57.9%) and renal (63.6%) causes as TPE indication
died whereas in neurologic and hematologic causes mortality were
lower (26.7% and 18.8%, respectively).
The median application regimen of TPE was 6 (range 2-33) sessions
with alternate days. In 32.3% of patients TPE had been performed
more than 10 times. The major adverse events were seen in 14
(23.3%) of patients (catheter related problems 6 patients, hypotension
3 patients, 1 catheter infection, 2 thrombocytopenia). One patient died
periprocedurely due to atrial fibrillation and myocardial infarction.
Conclusion: TPE is an effective therapeutic option for treating serious

manifestations of systemic autoimmune diseases with rare adverse
events. TPE could be a valuable option for those with refractory disease and/or concomitant infection,leucopenia. Patients with pulmonary and renal indications had increased mortality compared to patients
with hematologic and neurologic indications.
Family planning, fertility, pregnancy and

neonatal care
A097
INFERTILITY AND ASSISTED REPRODUCTIVE
TECHNOLOGIES: OUR EXPIRIENCE IN AUTOIMMUNE
DISEASES
Reggia R.1, Andreoli L.1, Lojacono A.2 and Tincani A.1
1
Spedali Civili and University of Brescia,Rheumathology and Clinical
Immunology,Brescia, Italy 2Spedali Civili and University of Brescia
Maternal-Fetal Medicine Unit,Department of Obstetrics and
Gynecology,Brescia, Italy
Introduction: Infertility is an important topic for Rheumatologists
because autoimmune diseases(AD) and related drugs can affect fertility
of patients.Moreover,an increasing number of women ask for the
evaluation of asymptomatic positivity for autoantibodies found in
the workup of the centers for the diagnosis and the treatment of
infertility.
Aim:To describe a case series of patients with fertility problems evaluated in our Clinic for Pregnancy in the Rheumatic Diseases.
Patients and Methods: We followed 36patients,27for preconception
counseling and 9pregnancy induced by assisted reproductive techniques (ART) (Table 1).
Results: The 9 prospectively followed pregnancies showed:-6(67%)
were induced by FIVET (In Vitro Fertilization Embryo
Transfer);1(11%) by Artificial Insemination, 1(11%) by IUI
(Intrauterine Sperm Injection);1(11%) OocyteDonation;-Pregnancies
prophylaxis: 5(56%) LMWHLDA; 1(11%) LMWH; 2(22%) LDA;
1(11%)without therapy;-No thrombosis nor disease flares during gestations; 1(11%)Ovarian Hyperstimulation Syndrome;Foetal-Maternal
complication in 62.5% of pregnancies: 2IUGR(Intrauterine Growth
Table 1. SLE: Systemic Lupus Erithematosus; PAPS: Primary Antiphospholipid Syndrom; UCTD: Undifferentiated Connective Tissue Disease; SjS: Sjogren
Syndrome; SS: Systemic Sclerosis; PA: Psoriasic Arthritis; AP: Anchylosing Spondylitis; LDA: Low Dose Aspirin; NSAIDs: Nonsteroidal Antinflammatory
Drugs; DMARDS: Disease Modifying Antirheumaticdrugs; PDN: prednison
DIAGNOSIS
MEAN AGE, [MEDIAN], (RANGE)
ADDITIONAL RISK FACTORS
TYPE OF DIAGNOSED INFERTILITY
CHRONIC THERAPIES
THYROID ALTERATIONS
AUTOANTIBODIES
INHERITED THROMBOPHILIA
ART ATTEMPTS FAILED IN THE PAST
27 INFERTILITY COUNSELING
9 FOLLOWED PREGNANCIES
2SLE;1PAPS;5UCTD;2SjS;1SS;2PA; 1AS;13isolated
Ab positivity.
38.5;[39];(19-39 years)
n22(81.5%):
Single:15(68%) Multiple:7(32%)
primary:25(93%),72%hidiopatic secondary:2(7%)
n10(37%):
LDA(80%);
NSAID(10%);
DMARDs(20%);
Levothyroxin(20%)
n9(33%)
n25(93%) single:44%;multiple:66% aPL:48%
53%(single:75% multiple:25%)
n56
15AI;38FIVET;3OocyteDonation
3SLA;2UCTD;1PAPS;1 Churg-Strauss, 1Takayasu,1 previous aPLpositivity.

35.5;[38];(29-40years)
n8(89%):
Single:7(87%) Multiple:1(13%)
primary:8(89%),75%hidiopatic secondary:1(11%)
n9(100%):
LDA(44%); DMARDs(44%);PDN(44%)
n2(22%)
n8(89%) single:22%;multiple:44%
25%(single:100%)
n2
2AI
aPL:44%
Lupus
490
Restriction);2PROM(Premature Rupture Of Membranes); 1preeclampsia; 1oligoidramnios, 1foetal-cardiac-malformation.
Conclusions: Most of the patients had additional risk factors and thyroid abnormalities, making it difficult to determine the role of autoimmunity in infertility;
Pregnancies induced by ART are often treated with a generous
prophylaxis, even in the absence of risk factors, in order to ensure
optimal outcomes;
Careful pharmacological prophylaxis during hormonal stimulation,
pregnancy and puerperium seems to prevent thrombotic complications;-Maternal-foetal-complications occurred in more than half of
the pregnancies, even if the risk of such cases is notoriously increased
in gestations induced by ART.
A098
LONG TERM OUTCOME IN CHILDREN BORN TO MOTHERS
WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND
ANTIPHOSPHOLIPID SYNDROME
Nalli C.1, Iodice A.2, Andreoli L.1, Lojacono A.3, Motta M.4, Fazzi E.2
and Tincani A.1
1
Spedali Civili and University of Brescia,Rheumatology and Clinical
Immunology,Department of Clinical and Experimental
Sciences,Brescia,Italy;2 Spedali Civili and University of Brescia,Unit of
Child and Adolescent Neuropsychiatry,Department of Clinical and
Experimental Sciences,Brescia,Italy;3 Spedali Civili and University of
Brescia,Obstetrics and Gynecology,Department of Clinical and
Experimental Sciences,Brescia,Italy;4 Spedali Civili,Neonatology and
NICU,Brescia, Italy
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune
disease that primarily affects women in childbearing age.
Antiphospholipid Syndrome (APS) is a systemic autoimmune disorder
defined by the occurrence of thrombosis and pregnancy morbidity in
presence of Antiphospholipid Antibodies(aPL).The long-term outcome and the neurodevelopmental outcome of children born to
patients with SLE and APS has been a matter of interest but only
few data are available.
Aim: To evaluate the neurodevelopment outcome in 33 children
(median age 6 years-old) born to mothers with SLE or APS with
IgGantiBeta2Glycoprotein I (aB2GPI) positivity during pregnancy.
All children were IgG-aB2GPI positive at birth.
Patients and Methods: A neurological physical exam was performed in
all children. We submitted some questionnaires to the APS/SLE
mothers: Child Behavior CheckList (CBCL)and an anamnestic
home-made set of questions obtained by a multidisciplinary
team(rheumatologists and pediatric neurologists)focused in particular
on maternal drugs during pregnancy, gestational age, baby developmental milestones, scholastic performances.Intellectual functioning
were performed with Wechsler scale for corrected age.
Results: In all children the neurological physical exam was normal. We
found a particular profile in 6 of these children(18%, all at term)in
which coexist mild behavior disorders(Attention Deficit Hyperactivity
Disorder and mood disorders),neurological manifestations(periodic
syndromes and seizures and headache)and learning difficulties(in the
nonverbal domain of functioning).All children showed a normal intelligence level.
Conclusions: This is the first study evaluating neurological manifestations in children born to aPL positive mothers with APS/SLE. The
results are overall reassuring on a normal intelligence, while some
minor disorders have been detected. These preliminary data must be
extended and compared with matched controls for sex and age.
References
1 Bomba M,Galli J,Nacinovich R,Cerebelli A.,Motta M,Lojacono
A,Fazzi E,Tincani A.2010 Sep-Oct.Neuropsychiatric aid in children
born
to
patients
with
rheumatic
diseases.Clin
Exp
Rheumatol.28(5):767-73.
2 Urowitz MB, Gladman DD,MacKinnon A,Ibanez D,Bruto
V,Rovet J,Silverman E.2008.Neurocognitive abnormalities in offspring of mothers with systemic Lupus Erythematosus.
Lupus:17(6):555-60.
A099
RESOURCE USE IN PREGNANT WOMEN WITH SYSTEMIC
LUPUS ERYTHEMATOSUS
Petri M.1, Daly P.2, and Pushparajah D.S.3
1
Johns Hopkins University School of Medicine, Baltimore, USA; 2Lupus
Foundation of America, Washington, USA; 3UCB Pharma, Brussels,
Belgium
Introduction: Physician communication with women with SLE considering a family is critical for improving their care and support.1
However, while it is understood that pregnant women with SLE
have higher rates of pregnancy complications,2 their use of medications
and hospital resources has not been extensively studied.
Aim: To compare resource utilization in pregnant women with SLE to
that in pregnant women without SLE and non-pregnant women with
SLE.
Patient and Methods: Review of records for women aged 12-54 years
using retrospective analysis of a US healthcare claims database from
20062012. SLE patients were isolated and pregnancies identified by
including codes for live birth, miscarriage, and ultrasound. Pregnant
women with SLE were matched 1:5 with pregnant women without
SLE, and non-pregnant women with SLE. Conditional logistic regression was used to calculate p-values.
Results: In comparison to pregnant women without SLE, pregnant
women with SLE spent a significantly higher number of days in the
maternity ward and required significantly more monitoring (Table 1).
Medication use and frequency of clinic visits was also significantly
different between pregnant women with SLE and non-pregnant
women with SLE (Table 2).
Reflecting these differences, healthcare costs were higher for pregnant
women with SLE compared to pregnant women without SLE and nonpregnant women with SLE (Tables 1-2).
Conclusion: Analysis of this large healthcare claims database shows
that healthcare of pregnant women with SLE is associated with
higher costs both during pregnancy and at delivery. This is predominantly due to increased fetal monitoring. Experts recommend more frequent rheumatologic visits during pregnancy for women with SLE,
however our analyses revealed an unexplained reduction in these
visits. As active disease is associated with higher rates of pregnancy
complications regular interaction with the SLE specialist should be
encouraged to ensure optimal management of both disease and
pregnancy.
References
1 Clowse et al Arthritis Rheum 2013 65(Suppl 10): S815.
2 Petri et al Arthritis Rheum 2013 65(Suppl 10):S1082.
Lupus
491
Table 1. Resource use for pregnant women with SLE compared to pregnant women without SLE
Resource Use [a]

Fetal echocardiographies
CVS/amnlocentesIs
Fetal stress and non-stress tests
Fetal ultrasounds
OBQYN visits
Days In the maternity ward
Mean Total All-Cause Direct Healthcare Cost* [b]
Pregnant Women with SLE (N1634)
Pregnant women without SLE (N8605)
0.7*
1.6
2.4*
5.9*
9.0*
2.8*
$21,509*
0.1
1.6
0.8
3.6
6.4
1.8
$11,481
ja] Average number of vIsHsflests d urlng the to week analysis period; jb] During the 44 week analysis period; *p<G.QQQ1 compared to Pregnant women
without SLE.
Table 2. Medication and resource use for pregnant women with SLE compared to non-pregnant women with SLE
Medication Use
NSAIDs
Methotrexate
Mycophenolate
Corticosteroids
Hydroxychloroquine
Resource Use [a]
GP visits
Outpatient hospital visits
Rheumatologlst visits
Internal medicine care provider visits
Mean Total All-Cause Direct Healthcare Costs [b]
Pregnant Women with SLE (N1634)
Non-pregnant Women with SLE (N8170)
28.9%*
1.7%*
3.9%*
39.7%*
42.8%*
24.1%
10.0%
19.8%
50.9%
53.8%
7.5*
8.4*
1.7*
1.2*
$20,665*
5.8
6.7
2.2
2.1
$12,591
[a] Average nu in ber of visit* d urlng the 44 week analysis period; jb] During the 44 week analysis
period; *p<C.CCC1 compared to non-pregnant women with SLE; Abbfrtlntfons NSAIDs, nonsteroidal anti-Inflammatory drugs; QP, general practitioner
A100
SYSTEMIC LUPUS ERYTHEMATOSUS AND PREGNANCY
OUR LAST 4 YEARS
Braga A.1, Vasconcelos C.2 and Braga J.1
Oporto Hospital Center, 1Obstetric Department, 2Clinical Immunology
Unit, Internal Medicine Department, Oporto, Portugal
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune
disease that affects women in childbearing age, so its association with
pregnancy is not a rare event. These pregnancies are full of challenges,
so multidisciplinary approach and specialized obstetric care are essential to assure the best outcome.
Aim: To analyze the clinical characteristics and outcomes of SLE pregnancies in our institution.
Patients and Methods: Retrospective descriptive study of all SLE pregnancies supervised by the same team at Autoimmune Disorders and
Pregnancy Consultation of Oporto Hospital Center, from January
2010 to September 2013.
Results: 44 pregnancies were included in 42 patients with a mean age of
31,4 years. 45 % were primiparous and 25 % had a history of miscarriage. 43% had SLE associated with other autoimmune diseases (15 %
with antiphospholipid syndrome) and 15 % had renal involvement. 95
% of cases continued the usual medication during pregnancy.

Hydroxychloroquine was the most widely used drug (64% of cases).
22,7 % had clinical or analytical worsening during pregnancy and 6,8
% postpartum. All cases were managed with adjustment of medication. 11,4% of cases had a preterm delivery, of which 60 % were iatrogenic preterm deliveries. There was an incidence of pre-eclampsia of
11,4% (60 % with severity criteria). 11,4 % of pregnancies were complicated with fetal growth restriction. The percentage of cesarean delivery was 40,9 %. There were no cases of fetal death, neonatal asphyxia,
major fetal malformations or severe neonatal morbidity. There was 1
case of neonatal lupus.
Conclusions: Pregnant SLE patients are a group of high risk pregnancies. A multidisciplinary approach with a pre-conception obstetric consultation is essential to prepare these patients pregnancy. Regular
specialized monitoring permits a early diagnosis of SLE exacerbations
or other obstetric complications and allow the institution of adequate
therapeutic options to assure the most favorable obstetric outcome.
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492
A101
WOMEN HEALTH ISSUES IN A ROMANIAN SYSTEMIC
LUPUS ERHYTEMATOSUS COHORT
Saulescu I., Vasile R., Opris D., Groseanu L., Borangiu A.,
Constantinescu C. and Ionescu R.
UMF Carol Davila Sf. Maria Hospital
Background: SLE is the prototype of autoimmune disease, affecting
especially women in the child-bearing age. The impact of the disease
will be on the fertility, but also will be related to menopause: early
menopause will contribute to accrual damage, like osteoporosis or
coronary heart disease.
Objective: to asses women health issues in SLE female patients and find
out the impact of the disease on their reproductive and hormonal
status, but also to quantify what they really know about this problems.
Material and methods: We evaluated 50 SLE female patients. They
answered a simple questionnaire. Before that all patients gave
informed consent to process the information. They were asked about
period characteristics, presence or absence of menopause, frequency of
gynaecologic check-up, methods of contraception, number of pregnancies and influence of SLE on family planning.
Results: Less then half go to a regular gynaecologic check-up, usually
after referral from other M.D. Three quarter of the patients is in menopause, 64% of them being in early or premature menopause. Only 6
patients from 25 being fertile are older then 40 years. Most used
contraceptive measures are local barriers. Except one pregnant patient,
rest of the fertile patients do not desire to have a child in the near
future. They associate pregnancy with a big risk, concerning their disease or child status. After being diagnosed with SLE, just 4 patients
accepted to continue their pregnancy.
Conclusion: SLE has a huge impact both on women physiology, but
also psychology, these being reflected on their reproductive status and
perception. Main characteristics of this cohort are menopause usually
before 45 years old and fearing of pregnancy. With a much shorter
fertile period, it seems to be very important for them to be counselled
on pros and cons pregnancy in every single case. Discussions about
post-menopausal co-morbities and preventions are also mandatory in
order to improve their quality of life.
Acknowledgments:
1. Stella Dali
2. Cristina Pamfil
Multidisciplinary, patient-oriented care

A102
CYCLOPHOSPHAMIDE AND RITUXIMAB COMBINATION
TREATMENT FOR SEVERE LUPUS IS EFFECTIVE AND WELL
TOLERATED
Shahzad A.1, Rizvi B.2, Jaffri F.2, Zhao X.3, Waldman M.3 and
Hasni S.1
1
NIAMS, NIH, Bethesda, MD; 2R-Research, Hamilton, NJ; 3NIDDK,
NIH, Bethesda, MD
Background: Systemic lupus erythematosus (SLE) is often complicated
by resistance or partial response to initial immunosuppressive regimen
and flares after initial response. There is limited data suggesting that
the combination of cyclophosphamide (CYC) and rituximab (RTX)
may have efficacy in recurrent and treatment resistant lupus. We present our experience with intravenous (IV) CYC plus RTX combination
and its comparison to CYC only therapy.
Methods: Data from patients who were treated with IV CYC monotherapy only or IV CYC and RTX combination from 2000-2013 was retrospectively reviewed. Patients demographic information, SLE duration,
SLE manifestations, co-morbidities, relevant labs, response to therapy
and post-treatment infections were recorded. Combination regimen was
prescribed based on clinicians discretion for recalcitrant SLE; most
commonly for recurrent flares of lupus nephritis. Predetermined definitions (based on published literature) were used to record flares (renal vs.
non-renal) and response (complete, partial or no response).
Results: A total of 43 SLE pts. with adequate follow up were identified:
31 (72%) received CYC; 12 (28%) received CYC plus RTX.
Indications for CYC and RTX combination treatment was lupus nephritis(10/12), CNS lupus(1/12) and treatment resistant SLE(1/12). There
was no difference in overall survival between CYC only and CYC and
RTX combo groups. In patients receiving combo treatment, median
duration of follow up was 36 months (6-50 months) prior to combo
treatment and 21 months (6-60 months) after receiving the combo
treatment. In the 12 patients who received CYC plus RTX, number
of flares before receiving CYC and RTX combo was significantly higher 38(Renal flares26; non-renal flares12) as compared to after
receiving combo13(Renal3; non-renal10). There was no significant increase in infections after receiving combo therapy.
Conclusion: CYC and RTX combination regimen may have efficacy in
reducing renal and non-renal lupus flares. This does not appear to be
associated with increased risk of infections. Our study has inherent
limitations due to its retrospective nature and small sample size.
A103
EFFECT OF TWO DIFFERENT EXERCISE PROGRAMS ON
CHRONIC FATIGUE IN SLE PATIENTS
Avaux M.1, Fraselle V.2, Nieuwland-Husson S.1, Hoellinger P.2,
Depresseux G.1 and Houssiau F.A.1
1
Rheumatology and 2Physical Medicine Departments, Cliniques
Universitaires Saint-Luc, Universite catholique de Louvain, Belgium
Objective: Chronic fatigue (CS) is a very common symptom in patients
suffering from systemic lupus erythematosus (SLE), even when the
disease is fully under control. It has been suggested that this condition
can be improved by exercice. In this 12-week study, we compared the
effects of a home training program without direct supervision (HT)
and a physiotherapist-supervised training (ST).
Methods: After signed informed consent, 42 consecutive patients with
inactive SLE suffering from CF, defined by a Krupps Fatigue Severity
Scale (FSS) >3.7, were randomly assigned the HT (n18) or ST
(n15) group, according to their place of residence. The program (3
times one hour/week) consisted in both groups of cardiotraining exercises (up the 60% of the maximal heart rate), followed by muscle
strengthening and stretching. The primary endpoint was the FSS at
week 12. A submaximal multistage cycle ergometer test was performed
at baseline and at week 12 to measure the physical working capacity at
75% of the predicted maximal heart rate per kg of body weight
(PWC75%/kg) as an index of cardiorespiratory endurance (fitness
index). Patients perception of exertion during this procedure was evaluated by Borgs scale. Nine additional SLE patients suffering from CF
who did not trained were similarly tested and served as a control
group.
Results: While the FFS did not change at Week 12 in the control
group, a significant improvement was noticed in both HT and ST
groups. Interestingly, compliance to the training program was similar
(48 and 54% of the expected hours in the HT and ST group, respectively). The PWC75%/kg did not change over time in none of the two
groups, not did patients perception of exertion during the cycle
Lupus
493
ergometer test. Interestingly, in the subgroup of HT and ST patients
who achieved a 50% observance rate with the program, Borgs scale
improved at week 12, thereby indicating that tolerance to exercise was
improved in compliant patients.
Conclusion: This study confirms the beneficial effects of exercise on CF
in SLE patients, although this was not associated to improvement of
the cardiorespiratory endurance at 3 months. Contrary to our working
hypothesis, the HT and the ST achieved similar positive results, probably because of a similar observance rates between the two groups.
Acknowledgements: The study was supported by a grant of the
Association Lupus Erythemateux (after a selection procedure performed by the Fonds pour la Recherche Scientifique en
Rhumatologie/ Fonds voor Wetenschappelijke Onderzoek in de
Reumatologie)
p0.036) even when controlling for other covariates (i.e., education,

disease duration, and neuropsychiatric involvement). This logistic
regression analysis also revealed that longer disease duration (adj.
odds ratio1.073; 95%CI: 1.012-1.137; p0.018) and neuropsychiatric
involvement (adj. odds ratio3.463; 95%CI: 1.338-8.965; p0.010)
remained statistically associated to cognitive involvement.
Conclusions: In addition to preventing lupus relapses and having
antithrombotic effects (1), HCQ appears to reduce the risk of cognitive
impairment in SLE.
References
1 Clin Rev Allergy Immunol. 2012;42:145-53.
A105
A104
HYDROXYCHLOROQUINE AND COGNITION IN SYSTEMIC
LUPUS ERYTHEMATOSUS
Cavaco S.1, Martins Silva Ana A.1,2, Santos E.1,2, Moreira Ines M.1,2,
Faria R.2, Marinho A.2, Almeida I.2, Farinha F.2 and Vasconcelos C.2
1
Servico de Neurologia, 2Unidade de Imunologia Clnica, Centro
Hospitalar do Porto/UMIB/ICBAS/UP, Porto, Portugal
Introduction: Available information on risk of cognitive impairment in
systemic lupus erythematosus (SLE) is limited and the possible effects
of hydroxychloroquine (HCQ) have not been explored yet, in opposition to its known favorable profile in others clinical manifestations.
Aim: To explore the association between HCQ and cognitive impairment in SLE.
Patients and methods: SLE was diagnosed according to ACR criteria
and patients taking HCQ had dosages between 100mg and 400mg/day.
A comprehensive neuropsychological battery (Nine-hole Peg Test,
Digit Span, Attentive Matrices, Corsi Test, Sentence Repetition,
Auditory Verbal Learning Test, Letter Word Fluency, Wisconsin
Card Sorting Test, Complex Figure Test, and Trail Making Test)
was applied to 140 patients with SLE (97.1% women; mean
age40.5, s.d.13; mean education10.7, s.d.5; mean age at
onset29.3, s.d.12.9; mean disease duration11.1 years, s.d.7.7;
31.4% with neuropsychiatric involvement) selected from the CHPs
Clinical Immunology Unit. The 5th percentile of regression based
adjusted norms (based on sex, age, and education coefficients of
healthy subjects) was used as cut-off of deficit on 18 neuropsychological measures. Patients with >3 neuropsychological measures
with deficit were considered to have cognitive impairment.
Experienced neuropsychologists blinded to the patients clinical records conducted the neuropsychological testing. Chi-square, MannWhitney test, and multiple logistic regression were applied for data
analyses.
Results: Cognitive impairment (19.3%) was significantly associated
with years of education (p0.014), disease duration (p0.002), and
neuropsychiatric involvement (11.5% vs. 36.4%; p0.001). No significant association was found with age (p0.058) or age at onset
(p0.614). The frequency of cognitive impairment was lower for
patients currently taking HCQ (12.6% vs. 33.3%; p0.004). The
odds of having cognitive impairment was significantly lower for
patients taking HCQ (adj. odds ratio0.368; 95%CI: 0.144-0.937;
LUPUS PATIENTS NEEDS AND PERSPECTIVES IN

SOUTHEASTERN EUROPE: DATA FROM THE CRETAN
LUPUS COHORT LETO
Kabouraki E.1, Rapsomaniki P.1, Terizaki M.1, Melissourgaki M.1,
Koutsogianni E.2, Starra A.2, Triantafillia K.2, Ploumidou N.2,
Sidiropoulos P.1, Bertsias G.1,3, Gergianaki I.1 and Fanouriakis A.1
1
Heraklion, Greece; 2 Arthritis Foundation of Crete, Greece; 3 Institute of
Molecular Biology-Biotechnology, FORTH, Greece
Background: As a result of rising medical costs and decreasing financial
resources, hospital stays and outpatient visits have become shorter,
challenging health practitioners to provide patients with complete
and adequate education and guidance. In chronic diseases such as systemic lupus erythematosus, self-management is considered a critical
element of care, which needs to be supported by a permanent educative
procedure. In this context, nursing instructions are a cornerstone in
influencing patient perceptions and facilitating self-care. In order to
provide instructions, nurses have to understand patients needs and
factors affecting those needs. Moreover, these instructions need to be
adjusted to the local culture. There is a paucity of such data in patients
living in Southern Europe.
Aim: To better understand the needs and perspectives of lupus patients
in a Southern European country.
Patients and Methods: A structured questionnaire has been developed
in collaboration with the patients association (Arthritis Foundation of
Crete). Issues addressed in the questionnaire include: patients beliefs
regarding the causes of lupus and the factors that influence the disease,
unmet needs related to physical (pain, fatigue), psychological and
socioeconomic issues, aspects of information-giving (including timing
and extent of information about prognosis and long-term risks), interest in self-management and telephone-based support, as well as gaps in
the collaboration of lupus physicians with primary care and specialty
physicians. A total of 50 patients were included in this survey.
Results and Discussion: The survey is in progress and results will be
presented during the meeting. Understanding lupus patients needs in
the local cultural and socioeconomic context will enable nurses to
interact more efficiently at the interface between physicians and
patients and help the latter gain empowerment over their disease.
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494
A106
MAPPING AND UTILIZATION OF HEALTH CARE SERVICES
FROM PATIENTS WITH NEWLY DIAGNOSED SYSTEMIC
LUPUS ERYTHEMATOSUS
Rapsomaniki P.1, Terizaki M.1, Kabouraki E.1, Melissourgaki M.1,
Koutsogianni E.2, Starra A.2, Triantafillia K.2, Ploumidou N.2,
Fanouriakis A.1, Bertsias G.1,3 and Gergianaki I.1,3
1
Heraklion, Greece, 2 Arthritis Foundation of Crete, Greece, 3 Institute of
Molecular Biology-Biotechnology, FORTH, Greece
Introduction: The course and usage of health care services of patients
with a new diagnosis of systemic lupus erythematosus (SLE) has not
been described in Greece, a country with a mixed health care system
combining public and private facilities and services.
Aim: To analyze the use of health care services and map the course of
patients from the time of first symptoms until the final diagnosis of
SLE in the island of Crete.
Patients and Methods: Patients (n50) with a first diagnosis of SLE
within the last 3 years were recruited from an open call from the
Arthritis Foundation of Crete. All patients underwent phone interview
through a structured questionnaire. Questions aimed to scrutinize the
entire journey within the health care system and included: timing
and type of first encounter with a health care service, number and
specialty of physicians until the diagnosis of SLE was reached, variety
of diagnostic tests ordered, and time to fist treatment after the onset of
symptoms. The impact of the disease on quality of life, family planning
and employment was also assessed.
Results and Discussion: This is an ongoing project and analysis will be
completed at the time of the meeting. Preliminary data suggest considerable delays along with significant unnecessary health care expenditures and a significant impact on quality of life and productivity.
Accordingly, an unmet need exists in increasing public awareness
around SLE, in order to curve unnecessary delays before expert rheumatologic consultation and institution of appropriate therapy.
A107
SOCIAL SUPPORT AND HEALTH-RELATED QUALITY OF
LIFE IN PATIENTS WITH ANTIPHOSPHOLIPID (HUGHES)
SYNDROME
Georgopoulou S.1, Efraimidou S.2, MacLennan S.J.3, Ibrahim F.1 and
Cox T.4
1
Academic Department of Rheumatology, Kings College London,
London, United Kingdom, 2Department of Psychology, University of
Nottingham, Nottingham, United Kingdom, 3Academic Urology Unit,
University of Aberdeen, Aberdeen, United Kingdom, 4Centre for
Sustainable Working Life, Birkbeck University of London, United
Kingdom
Introduction: Antiphospholipid (Hughes) syndrome (APS) is characterized by recurrent venous and arterial thrombosis, miscarriage, neurological features such as stroke, headache, fatigue, memory loss, and
epilepsy1,2. Little is known about the physical and psychological
burden of this long-term condition.
Aim: To investigate the relationship between social support and healthrelated quality of life (HRQOL) in patients with antiphospholipid
(Hughes) Syndrome.
Patients and methods: 270 APS patients with a clinical diagnosis of
APS participated in a cross-sectional online questionnaire survey
worldwide. Response rate was 60%. Data included social support
(instrumental, emotional and informational), HRQOL (SF-36), demographics and disease-related information.
Results: Multiple regression analysis indicated that specific types of
social support were predictive of particular HRQOL domains.
Emotional support predicted positive mental health (R2 0.02,
adjusted R2 0.02, F(1, 266) 6.34, p < 0.05). Lower instrumental
support was a significant predictor of positive daily active (R2 0.05,
adjusted R2 0.04, F(1, 262) 12.79, p < 0.001), vitality (R2 0.04,
adjusted R2 0.03, F(1, 265) 9.44, p < 0.05), body pain (R2 0.04,
adjusted R2 0.04, F(1, 261) 11.60, p < 0.001), and general health
(R2 0.02, adjusted R2 0.02, F(1, 265) 6.03, p < 0.05). Both lower
instrumental and informational support provision significantly predicted increased physical limitations (R2 0.06, adjusted R2 0.05,
F(1, 267) 7.78, p < 0.001).
Conclusions: Insufficient social support was predictive of limitations in
various HRQOL domains in patients with APS. The need for patienttailored interventions incorporating a bio-psychosocial approach is
highlighted. These interventions would address psychosocial aspects
of antiphospholipid (Hughes) Syndrome with the aim to improve
patients psychological and physical status.
References
1 Hughes GRVHughes Syndrome: A Patients Guide. SpringerVerlagLondon.
2 Hughes G. Migraine, memory loss, and multiple sclerosis.
Neurological features of the antiphospholipid (Hughes)
syndromePostgrad Med J 2003; 79: 8183.
Miscellaneous - Difficult cases

A108
A CASE OF SYSTEMIC LUPUS ERYTHEMATOSUS AND
REFRACTORY BILATERAL PLEURAL EFFUSION AND
REVIEW OF THE LITERATURE
Karageorgas T.1, Triantafillidou Ch.2, Anastasopoulos A.2,
Dimakou K.3, Toumbis M.2 and Boumpas D.T.4
1
General Hospital of Athens G.Gennimatas, Rheumatology
Department, Athens, Greece, 2General Chest Diseases Hospital of
Athens Sotiria, 6th Department of Respiratory Diseases, Athens,
Greece, 3 General Chest Diseases Hospital of Athens Sotiria, 5th
Department of Respiratory Diseases, Athens, Greece, 4 National and
Kapodistrian University of Athens, Medical School, Athens, Greece
Introduction: Pleuritis with or without pleural effusion is the most
common respiratory manifestation in Systemic Lupus Erythematosus
(SLE) occurring in approximately 45% of patients. Treatment with
moderate/high steroid dose and immunosuppressives is effective in
almost all cases of lupus pleuritis.
Case description: A 31 year-old female patient was diagnosed with SLE
a year ago based on the presence of malar rash, photosensitivity, arthritis and bilateral pleural effusion. ANA titer of 1/320 and anti-SSA/
Ro antibodies were detected. Pleural effusion was exudative with
lymphocytic predominance, normal glucose and high protein and
LDH levels. A complete workup for other causes of pleural effusion
including infection and malignancy yielded negative results. The
patient was treated with prednisolone (0.5mg/kg/day), hydroxychloroquine 400mg/day and azathioprine 2mg/kg/day with resolution of her
symptoms. However pleural effusions recurred requiring repeated
drainage and increased steroid doses with no evidence of improvement.
After one year of follow-up the patient was still symptomatic with
pleuritic chest pain and 3/4 in the MRC scale of dyspnea. Based on
Lupus
495
the absence of SLE activity from other systems, the patient was
referred for talc pleurodesis.
Discussion and Literature Review: Cases of refractory lupus pleural
effusions are rarely reported in the literature, thus definite recommendations for the management of such cases is impossible to formulate.
In case of refractory pleural effusion and severe multisystemic lupus
activity treatment with high dose steroids and immunosuppressive
therapy is usually employed. In cases where pleural effusion (as in
our case) represents the sole active manifestation of SLE, topical treatment with pleurodesis and/or pleurectomy should be considered.
However more data are needed on the long-term efficacy and complications of these measures.
A109
CHYLOUS ASCITES IN SYSTEMIC LUPUS ERHYTEMATOSUS
CASE PRESENTATION
Vasile R. and Saulescu I.
UMF Carol Davila Sf. Maria Hospital, Bucharest, Romania
Intoduction and Aim: We describe a rare case of Systemic Lupus
Erythematosus (SLE) with cutaneus, articular, haematological,
immunological, renal and serous manifestations, which presents
within the serous involvement: recurrent chylous ascites. Chylous ascites has rarely been described in patients with SLE, only 5 cases being
reported in literature at the moment, this one being apart from the
reported ones.
Case description: The laboratory analysis of the perithoneal fluid in our
patient indicated high levels of triglycerides, high number of leucocytes,
positive antinuclear antibodies, low complement levels consistent with
chylous ascites in SLE patients. The lab investigations of the fluid
excluded malignancy (hematological or solid) or infections (including
tuberculosis).
Discussion and Literature Review: Compared to the other cases
described, this patient presented recurrent ascites, while she was
under different courses of treatment. She had in her history repeted
abdominal surgical interventions before diagnose of SLE was established. In addition to her chronic illness the patient was exposed to
Hepatitic Virus B, and developed viral hepatitis, being now on lamivudine treatment for almost 2 years. Apart from presenting the course
of the disease, laboratory findings and possible differential diagnosis
for the chylous ascites, we will discuss the optimal course of treatment
in this particular case, taking into consideration the evolution of the
disease and the added pathology.
of our knowledge, there have been only 3 published case reports

describing the co-existence of these two autoimmune diseases in children (3,4,5). We recently diagnosed and treated 2 children with
Juvenile-onset Systemic Lupus Erythematosus (JSLE) and Juvenile
Myasthenia Gravis (JMG).
To increase awareness of the coexistence of these 2 rare conditions, we
have collectively reviewed the clinical characteristics of 2 of our cases
with 3 cases in the published literature.
Case description: All 5 patients were female. Mean age at the time of
diagnosis of JSLE and JMG were 10 (6 13) years and 12 (10 13)
years respectively. In 4/5 cases, symptoms of JMG preceded the symptoms of JSLE. Ethnicities of the 5 cases were: 2 Caucasian, 2 Asian and
1 Arab. JSLE and JMG manifestations in these patients are described
in Table 1. Treatment for JSLE included glucocorticosteroids in all 5
patients, mycophenolate mofetil in 2/5, cyclophosphamide in 1/5 and
hydroxychloroquine in 1/5. JMG was treated with pyridostigmine in
all 5 patients, plasmapheresis in 3/5, intravenous immunoglobulin in 2/
5 and thymectomy in 2/5. In the short-term, therapies achieved remission of JMG symptoms in 4/5.
Discussion: In children, association of JSLE and JMG is rare.
Although diagnosis of JSLE preceded JMG in 3/5 cases, 4/5 recalled
episodic symptoms attributable to JMG prior to their JSLE symptoms.
All 5 patients had the generalised form of JMG at presentation. Here
we have combined our two cases with 3 published cases to describe the
clinical characteristics of these rare associations.
Table 1. Clinical characteristics of two new patients, and combined for all
five reported cases to date
ACR revised criteria for
classification of systemic
lupus erythematosus
Patient 1
Combined for all 5 patients

Patient 2 reported to date
Malar rash
Yes
Yes
2/5(40%)
Discoid rash
No
No
0/5
Photosensitivity
Yes
No
1/5(20%)
Oral ulcers
No
No
1/5(20%)
Non-erosive arthritis
Yes
Yes
5/5(100%)
Pleuritis or Pericarditis
Yes
No
3/5(60%)
Renal disorder
No
Yes
3/5(60%)
Neurologic disorder
No
No
1/5(20%)
Hematologic disorder
Yes
Yes
3/5(60%)
Immunologic disorder
Yes
Yes
5/5(100%)
Positive anti-nuclear antibody
Yes
Yes
4/4 tested (100%)
Features of Myasthenia Gravis
Patient 1 Patient 2 Combined for all 5

patients reported to date
Generalised muscle weakness
Yes
Yes
5/5 (100%)
Bulbar muscle weakness
Yes
No
2/5(40%)
Anti-cholinesterase antibodies
Yes
Yes
5/5 (100%)
Edrophonium challenge positive Yes
Yes
4/4 tested (100%)
Electromyogram positive
Yes
3/3 tested (100%)
Yes
A110
CO-EXISTENCE OF JUVENILE-ONSET SYSTEMIC LUPUS
ERYTHEMATOSUS AND JUVENILE MYASTHENIA GRAVIS
Sampath S.1,4, McDonagh J.2, Cleary G.1, Spinty S.3, Pain C.1,
Baildam E.1, Beresford M.1,4 and McCann L.1
Alder Hey Childrens NHS Foundation Trust, Department of Paediatric
Rheumatology 1 and Department of Paediatric Neurology 3, Liverpool,
UK.2 Birmingham Childrens Hospital NHS Foundation Trust,
Department of Paediatric and Adolescent Rheumatology, Birmingham,
UK, 4University of Liverpool, Department of Womens and Childrens
Health, Institute of Translational Medicine, Liverpool, UK.
Introduction: Co-existence of Systemic Lupus Erythematous (SLE) and
Myasthenia Gravis (MG) has been reported in adults (1,2). To the best
References
1 Jallouli M, Saadoun D, Eymard B, et al. The association of systemic lupus erythematosus and myasthenia gravis: a series of 17
cases, with a special focus on hydroxychloroquine use and a
review of the literature. Journal of neurology 2012, Jul;
259(712907.
2 Sthoeger Z, Neiman A, Elbirt D, et al. High prevalence of systemic
lupus erythematosus in 78 myasthenia gravis patients: a clinical and
serologic study. The American journal of the medical sciences 2006,
Jan; 331(149.
3 Omar H, Alzahrani M, Al Bshabshe A, et al. Systemic lupus
erythematosus after thymectomy for myasthenia gravis: a case
report and review of the literature. Clinical and experimental nephrology 2010; 14(32726.
Lupus
496
4 Nishimura A, Yamazaki H, Fuchigami T, et al. A childhood case
of systemic lupus erythematosus associated with myasthenia gravis.
No To Hattatsu 1997; 29(53905.
5 Rosskamp R, Berdel D. Myasthenia gravis following lupus erythematosus disseminatus. Klin Padiatr 1983, Nov-Dec; 195(64335.
A112
A111
Introduction: Dystrophic calcinosis is often noted in the subcutaneous

tissues of connective tissues diseasesprimarily systemic lupus erythematosus, scleroderma, or dermatomyositis. Here we report an uncommon case of dystrophic calcinosis cutis associated with generalised
morphoea that led to below knee amputation for arterial insufficiency
and cramps.
Case report: In 1996 a 29-year-old male was referred to our dermatology department by his general practitioner with a 5 year history of
sclerotic discoloured plaques on multiple sites and patchily on both
legs with almost circumferential involvement of the left calf and ankle.
Movement in the latter was restricted. His general health was good.
Histopathological examination of a skin biopsy confirmed the diagnosis of morphoea. His blood count, hematocrit, ESR, random blood
sugar, urea, creatinine, sodium, potassium and liver function tests
were normal. Anti-nuclear antibodies, anti dsDNA, rheumatoid
factor and serologies for HIV and Borrelia were not reactive. The
patient was started on oral prednisolone with penicillamine 250mg
daily and with bath PUVA and for the next 15 he has tried several
treatments such as penicillamine, hydroxychloroquine, calcitriol, with
no improvement. In the meanwhile, he developed asteatotic eczema on
his left leg with secondary infection and after several years his most
delibating symptom was severe muscle spasm/cramps on his lower left
leg. In 2002, on examination there was calcinosis cutis on the shin of
his left leg developed. In March 2012, he was to have amputation of his
left lower leg because of the cramps, his considerably atrophy of his left
lower leg with abnormal skin with tension to erode and very poor
circulation. In August 2012, he experienced left below knee amputation. Because of the calcinosis cutis he could not wear a below-knee
prosthesis and he was restricted to a wheelchair.
Conclusions: Patients with morphoea may experience delay in diagnosis, which likely impacts outcome. Sometimes, calcinosis cutis could be
a sequel of morphoea. In this exceptionally unusual case the patient
required amputation.
DIFFUSE SPLEEN CALCIFICATION IN A PATIENT WITH

SYSTEMIC LUPUS ERITHEMATOSUS (SLE)
Rumbullaku M., Fiorucci M.C., Cagnati P., Pupo F., Pesce G.P.,
Puppo F. and Bagnasco M.
Department of Internal Medicine, University of Genoa, Genoa, Italy.
Introduction: Spleen calcifications in SLE have been reported in a small
number of patients, with a unique pattern, and their significance in this
disease is reason of debate.
Case description: we report the case of a 34 year-old Caucasian woman
in who SLE was diagnosed at the age of 13, when she presented with
rash, fever, and intermittent arthritis. Antinuclear antibody (ANA) test
was positive (1:640), with a homogeneous pattern, and anti-doublestranded (ds) DNA antibodies were present. C3 and C4 levels were
reduced. Anti-phospholipid antibodies and lupus anticoagulant were
negative. She was initially treated with steroids, azathioprine and
hydroxychloroquine, then was switched to mycophenolate mofetil
and currently she is on low-dose steroids.
During this time, she had many flares with haematological and kidney
involvement. In 2010, in conjunction with a flare, ultrasound scan was
performed and splenic microcalcifications were found. Two years
before this observation she had had an abdomen echography for
abdominal pain and, in this examination, the spleen was normal without any calcification. In 2011 she had another disease flare with haematological and kidney involvement and was treated with
cyclophosphamide and steroids, but she had severe side effects (leukopenia and fever). Tacrolimus was then administered to obtain a gradual improvement of proteinuria and systemic symptoms. Abdominal
ultrasound scans were performed and confirmed the presence of splenic
microcalcifications. In 2012 the disease was controlled with low dose
steroids and an abdominal CT scan showed that multiple intraparenchimal splenic microcalcifications were unchanged.
Discussion: SLE is a multisystem autoimmune disease that affects various organs, including the spleen. In the last years massive splenic
microcalcifications with an unique pattern have been observed in few
patients with SLE and it was reported they were not the consequence
of comorbidities usually inducing splenic calcifications. We speculate
that in this patient spleen calcifications may represent an unusual
immunological reaction of the spleen during SLE flares.
DISABLING GENERALISED MORPHOEA ASSOCIATED WITH

CALCINOSIS CUTIS: UNUSUAL CASE AND MANAGEMENT
CHALLENGES
Koumaki D. and Grattan C.E.
Department of Dermatology, Norfolk and Norwich University Hospital,
University of East Anglia, Norwich, United Kingdom
References
1 Fett NM. Morphea (Localized scleroderma). JAMA Dermatol
2013 Sep; 149(91124.
2 Johnson W, Jacobe H. Morphea in adults and children cohort II:
patients with morphea experience delay in diagnosis and large variation in treatment. J Am Acad Dermatol 2012 Nov; 67(5881889.
3 Yamamoto A, Morita A, Shintani Y, Sakakibara S, Tsuji T.
Localized linear scleroderma with cutaneous calcinosis. J Dermatol
2002 Feb; 29(2112114.
Lupus
497
A113
HYPERTROPHIC CUTANEOUS LUPUS ERYTHEMATOSUS: A
DIAGNOSTIC PITFALL
Walsh N.M.1, Green P.J.2 and Hanly J.G.3
Dermatopathology1, Dermatology2, Rheumatology3, Capital District
Health Authority and Dalhousie University, Halifax, Nova Scotia,
Canada.
Introduction: Hypertrophic cutaneous lupus erythematosus (HCLE),
an uncommon variant of discoid lupus erythematosus (DLE), is a
challenging diagnosis. Its clinical presentation as verrucous nodules
or markedly hyperkeratotic plaques on the extensor surfaces of the
extremities and/or the face, and accompanying histopathological features simulate squamous cell carcinomas and actinic keratoses.
Aim: We studied our collective experience of this rare entity over the
past decade, to establish whether existing awareness of its challenging
nature is sufficient to avert medical error.
Patients and methods: Patients with HCLE were identified via clinical
records in Rheumatology and Dermatology and cross referenced with
those in Pathology. Demographic, clinical and pathological data were
reviewed.
Results: Seven patients [2 men and 5 women] with HCLE were identified. The mean age was 49 years (range 30-61). In 4 patients with
systemic lupus erythematosus (SLE), 3 had previously documented
DLE and were under the care of a dermatologist and/or a rheumatologist. The remaining 3 patients were managed by plastic surgeons. The
hyperkeratotic nodules and plaques of HCLE were located on the face
in 4 cases and on the extremities in 3. Biopsies were undertaken in 5
cases because of a clinical suspicion of malignancy and in 2 due to
diagnostic uncertainty. In 3 patients an erroneous clinical and pathological diagnosis was made prior to recognition of HCLE: 2 were
diagnosed with squamous cell carcinomas in the perioral area resulting
in inappropriate surgery; the other was diagnosed with psoriasis.
Conclusion: In this series from an academic medical centre there was a
failure to recognize and appropriately treat HCLE in 3 of 7 patients
upon initial presentation. Despite cautionary evidence in the literature,
HCLE continues to elude diagnosis, thereby leading to delayed medical intervention or inappropriate surgery.
A114
LUPUS IN MEDICAL EDUCATION: STUDENT AWARENESS
OF BASIC, CLINICAL AND INTERDISCIPLINARY ASPECTS
OF COMPLEX DISEASE PROCESSES
Kerezoudis P.1, Lontos K.1, Apostolopoulou A.1, Christofides A.1,
Letsos A.2, Leventis D.2, Banos A.1, Fanouriakis A.2, Frangou E.1,
Sidiropoulos P.2, Bertsias G.2, Boumpas D.T.1 and Johnson E.1
1
Medical Schools National and Kapodistrian University of Athens,
2
University of Crete
Introduction: The transition from learning to the development of diagnostic and treatment competence remains a challenge in medical education. Linking the preclinical curriculum to clinical practice and
exposing students to the multi- and interdisciplinary aspects of medical
care may enhance students understanding of the core components of
disease processes. The diagnosis and treatment of disease processes
with a complex pathophysiology, such as systemic lupus erythematosus
(SLE) requires a multidisciplinary approach that embraces basic and
clinical science concepts from various disciplines and may serve as an
educational model system.
Aim: The objective of this study was to investigate the impression of
students regarding the integration of basic and clinical science
knowledge from various disciplines with regards to one complex disease, SLE.
Methods: A survey approach was used to appraise responses from
students (N200) during preclinical studies (N100) and early in
their clinical training (N100) in two medical schools in Greece
(Universities of Athens and Crete). A structured questionnaire assessed
the students understanding of core concepts in basic immunology, as
well as basic knowledge in other relevant disciplines, including rheumatology, dermatology, nephrology, psychiatry, cardiology, among
others. In addition, the students perceptions about the etiology of
lupus and factors that influence the course of the disease and management were also addressed.
Results and Discussion. The findings of this study will highlight the
extent to which a multidisciplinary exposure to SLE that expands
basic to clinical science enhances learning outcomes in medical
education.
A115
LUPUS PNEUMONITIS WITH ACUTE RESPIRATORY
DISTRESS SYNDROME AS INITIAL MANIFESTATION OF SLE
Felea I.1, Antal O.2, Ghib L.1, Andrei M.1, Hagau N.2 and Rednic S.1
1
Rheumatology Department, 2Anesthesia and Intensive Care Unit
Department, Cluj County Emergency Hospital, Cluj Napoca, Romania
Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiple organ involvement. Lung involvement
usually appears later in the course of disease. Acute lupus pneumonitis
is a rare manifestation with incidence raging from 1 to 12%. We present a case of lupus myocarditis and acute pneumonitis complicated
with acute respiratory distress syndrome (ARDS) as the initial manifestation of SLE.
Case description: A 29 years old female patient was referred to our
hospital with a diagnosis of sepsis 21 days after a cesarian section
performed for late onset preeclampsia. Upon admission she had dyspnea with 40 breaths/minute, SaO2 98% with FiO2 0.5, fever, bilateral
lower limb edema, elevated blood pressure (150/90mmHg). Pulmonary
X-rays showed bilateral basal infiltrates and massive pleural effusion.
Laboratory tests revealed anemia, high inflammatory markers, hypoproteinemia with hypoalbuminemia and nephrotic range proteinuria.
CT exam raised the suspicion of ARDS or bilateral pneumonic processes. Her condition gradually worsened despite intravenous antibiotics and anticoagulation and 20 days after admission she developed
respiratory failure, signs of heart failure due to acute myocarditis needing endotracheal intubation and mechanical ventilation. The patient
was transferred to the ICU department. Pulmonary alveolar hemorrhage was excluded by bronho-alveolar lavage and cultures were negative. Immunological tests showed homogenous ANAs 1/2000, high
titre anti DNAds antibodies, low C3 levels, positive ACL antibodies.
A diagnosis of SLE was made. Pulse intravenous metilprednisolone
and Cyclophosphamide along with Levosimendan (calcium sensitiser)
were administered with resolution of the pulmonary infiltrates,
improvement of cardiac function and extubation after another 15 days.
Discussion: ARDS caused by lupus pneumonitis is a rare entity and
difficult to recognize. Because of the late recognition of lupus pneumonitis, especially as a first manifestation of SLE, mortality is high.
Aggressive treatment can lead to a favorable outcome. In young
patients with non- infectious alveolar infiltrates a diagnosis of lupus
pneumonitis should be considered.
Lupus
498
A116
PULMONARY HEMOSIDEROSIS AN UNUSUAL CASE
Cagnati P., Fiorucci M.C., Rumbullaku M., Pupo F., Bagnasco M. and
Puppo F.
Department of Internal Medicine, University of Genoa, Genoa, Italy
Introduction: Pulmonary hemosiderosis is a rare condition characterized by recurrent episodes of diffuse alveolar hemorrhage that may
lead to lung fibrosis. It usually reveals with dyspnea, hemoptysis and
secondary iron deficiency anemia. The diagnosis is established by
revealed hemosiderin-laden macrophages in broncho-alveolar lavage
(BAL) or open lung biopsy.
Case description: We reported the case of a 57 years-old female suffering from undifferentiated connective tissue disease associated with
anti-phospholipid antibodies syndrome. She had positivity for antinuclear (ANA) antibodies with a speckeld pattern (1:160), anti-cardiolipin and anti-b2-glycoprotein-1 antibodies as well as lupusanticoagulant activity at high titers since 2006.
Since 2006 the patient reported low-grade fever, lymphadenopathy,
arthralgias and several pericarditis episodes. She started a therapy
with hydroxychloroquine (HCQ) 200 mg, steroids and low dose
acetyl salicylic acid. Later the patient was treated with azathioprine
until 2009 when she showed segmental deep thrombophlebitis. For this
reason, she added to HCQ dicoumarol and mycophenolate mofetil
(MMF). This combined therapy allowed remission of systemic manifestations and thrombophilia. In 2011 the patient withdrew HCQ
because of ossesive-compulsive syndrome. Two months later she
reported abdominal pain, precordial tightness, anorexia, arthralgias
and few episodes of hemoptysis. The physical examination revealed
and a tense abdomen and pain to small and medium-sized joints of
the limbs. The blood tests showed hypochromic anemia and low ferritin. Therefore MMF was discontinued. Colonscopy and scintigraphy
with labeled blood cells resulted negative and gastroscopy revealed
hiatal hernia in the absence of gastric mucosal lesions. Computerized
tomography demonstrated signs of emphysema rarefaction and bronchoscopy with BAL showed the presence of many hemosiderin-laden
macrophages.
Discussion: These findings lay a diagnose of pulmonary hemosiderosis
related to autoimmune disease. The classical therapy with high doses of
corticosteroids was not possible in our case due to the patients psychiatric symptoms. Then we treated the patient with MMF leading to
clinical response. The patient is now asymptomatic.
A117
SYSTEMIC LUPUS ERYTHEMATOSUS ASSOCIATED WITH
CASTLEMANS DISEASES. CASE PRESENTATION AND
REVIEW OF LITERATURE.
Shalaby M.A.F.1 and Jamil A.2
1
King Khalid University.Faculty of Medicine, Medical Dept, KKU,
Abha, KSA, 2King Khalid University.Faculty of Medicine Pathology
Dept, KKU, Abha, KSA
Introduction: Systemic lupus erythematosus is an autoimmune disorder
which affects mainly young adult females. Many organ can be affected
in SLE like renal, musckuloskeletal, central nervous system and others
with apparent constitutional symptoms. Lymphadenopathy is another
common manifestation in active lupus and the cumulative incidence of
at some point is high, up to 60% [1]. The differential diagnosis for
diffuse lymphadenopathy is extensive, including infection, malignancy,
and autoimmune or connective-tissue disease [2]. Castlemans disease
(CD) is characterized by reactive lymphadenopathy with chronic

inflammation, [3] and manifests as angiofollicular lymph node hyperplasia, striking interfollicular vascularity and dense interfollicular
plasma cell type and/or eosinocytosis.[4] had been rarely associated
with autoimmune connective tissue disease. A few cases had been
reported with Systemic Lupus Erythematosus, Rheumatoid Arthritis,
Myasthenia gravis and Sjogren Syndrome.
Patient: We present a case that fulfills the ACR criteria for SLE that
responded to medical therapy but when flared with generalized lymphadenopathy proved to have CD.
Conclusion: The association of the CD with SLE is rare but because of
the complexity of SLE and its broad differential diagnoses, those SLE
patients who showed atypical presentation or with progressive adenopathy another overlooked underlying disease should be considered and
one of them is Castlemans disease.
References
1 Xia JY, Chen XY, Xu F, et al. A case report of systemic lupus
erythematosus combined with Castlemans disease and literature
review. Rheumatol Int . 2012 Jul; 32(7218993) :.
2 Roberts J, Puerantz A, Leo L, Systemic Lupus Erythematosus with
Features of Castleman Disease. Musculoskeletal Medicine J. Feb 8,
2012.
3 Castleman B, Iverson L, Menendez VP. Localized mediastinal
lymph node hyperplasia resembling thymoma. Cancer 1956; 9:
82230.
4 Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and
plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 1972; 29: 67083.
A118
SYSTEMIC LUPUS ERYTHEMATOSUS AN
INTERDISCIPLINARY CHALLENGE
Karnebeck V. and Fiene B.
Ernst-Moritz-Arndt-Universitat Greifswald, Germany
Introduction and Aim: Treatment of systemic lupus erythematosus
patients is sometimes challenging and requires an interdisciplinary
approach.
Case description: Here we report a 43 years old male patient who presented with progressive tetraparesis and right prefrontal cerebral
changes in MRI in the neurology department.Several differential diagnoses regarding those cerebral abnormalities were rouled out until a
cerebral biopsy confirmed Lupus vasculitis.Further diagnostic revelead
an isolated CD4-lymphopenia, which has been reported to be an
extreme rare disease, sometimes seen in autoinflammatory diseases.
Due to this lymphopenia initial immunosuppressive treatment was
delayed.Additionally positive aquaporin 4-antibodies could be
detected which are seen in neuromyelitis optica, so-called Devic
syndrome.After intensive interdisciplinary discussion with decided to
treat this patient with cyclophosphamide intravenously in combination
with steroids, antimalarials and vitamin D.The patient recovered, tetraparesis was solved and after remission he has been treated with
belimumab.
Discussion: This case is illustrative due to the combination of several
rare manifestations which offered several different therapeutic strategies. In this poster we describe the diagnostic work-up and decision
processes involving different medical specialties.
Lupus
499
A119
SYSTEMIC LUPUS ERYTHEMATOSUS IN A PATIENT WITH
SICKLE CELL DISEASE
Tazi Mezalek Z.1,2, Maamar M.1,2, Harmouche H.1,2, Bachir H.1,
Ammouri W.1 and Adnaoui M.1,2
1
Rabat, Maroc; 2Internal Medicine departement, Ibn Sina University
Introduction: Sickle cell disease (SCD) is a prevalent genetic disorder
that includes sickle cell anemia the homozygous and most common
form of SCD (SS), sickle cell hemoglobin C (SC) and sickle cell b
thalassemia (S/b thal). The occurrence of connectivite tissue diseases
in particular systemic lupus erythematosus (SLE) has been rarely
reported in SCD patients. Due to similar clinical manifestations, the
diagnosis of SLE in patient with SCD may be difficult and often
delayed. We report one patient who developed symptoms initially
attributed to the SCD but in whom further investigations revealed
an underlying SLE.
Observation: A 23 year-old woman without family story of SCD was
admitted in department of internal medicine for anemia, bone pain,
arthralgia and fever. Symptoms had been developing for 6 weeks with
alteration of general condition and abdominal pain. On physical examination the patient was pale without jaundice, she had a temperature of
39 5C, blood pression was 130/75 mmHg and heart rate was 100/min.
There is a slight splenomegaly, pain to the pressure of long bones and
arthritis in knees. Blood tests results showed normocytic anemia at 6.6
g/dl with high reticulocyts count (230000/mm3), hyperleukocytosis
with granulocytosis (leucocyt count 16500/mm3, PNN 9500/mm3)
and moderate thrombopenia (100000/mm3). Further investigations
showed diminished haptoglobin (0.08 mg/l), elevated lactodeshydrogenase (4670 UI/l) indirect hyperbilirubinemia (21 mg/l) with moderate
cytolysis and cholestasis (ASAT 43 U/l, ALAT 65U/l, PAL217 U/l and
gGT 188 U/l). Hemoglobin electrophoresis test showed Hb S at 50.3%,
Hb C at 44% and Hb A1 at 0% confirming the diagnostic of SCD
(hemoglobin S/C).
Erythrocyt sediment rate was 110 mm first hour, C-reactive protein 38
mg/l (range <6 mg/l), fibrinogen 6.4 g/l (24 g/l) and serum protein
electrophoresis showed a polyclonal Ig G 24 g/l (range 913 g/l) with
normal immunofixation.
Blood cultures were negative, tuberculin skin test was at 8 mm.
Serology for human immunodeficiency virus, Hepatitis B, Hepatitis
C, brucellosis and typhoid fever were all negative. Cytobacteriologic
urine analysis revealed no bacteria but microscopic hematuria
(670/mm3) and leucocyturia (50/mm3). Proteinuria was negative.
Chest X ray examination was normal. Abdominal ultrasonography,
thransthoracic and transesophageal echocardiography were also
normal. Thoraco-abdominal scan revealed numerous splenic infarctions. Bone scan showed diffuse bone infarcts. Instead, the evolution
was marked by the development of other arthritis in hands and relapse
of anemia. The coombs test performed on admission and received later
was strongly positive (IgG). Immunological investigations revealed a
positive anti-nuclear antibody (1/2600), positive anti-Sm. Anti-phospholipid antibodies were negative. The diagnosis of SLE associated to
SCD was established with five criteria of American College of
Rheumatology. Steroids were administered at a pulse of methyprednisolone 1g/day for 3 days followed by oral prednisone at 1 mg/kg/day
with hydroxychloroquine. Her symptoms have quickly improved. At
18 months follow up, she is in clinical remission on prednisone 5 mg

per day, she has not sickle cell crisis and SLE is actually quiescent.
Discussion: The overlap of SLE and overt SCD is of interest but the
limited number of patients that have been reported previously implies
that the association is uncommon. Forty similar cases have been
reported in the literature over the last 50 years. This report illustrates
the importance of considering associated diseases when clinical findings are unexplained by SCD alone or are unresponsive to the conventional treatment. Early diagnosis and the initiation of appropriate
treatment may decrease morbidity and mortality in these patients.
A120
TINEA CAPITIS OVERINFECTION OF CUTANEOUS
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) UNCOVERED BY
RITUXIMAB
Alves R., Faria R. and Vasconcelos C.
Unidade de Imunologia Clnica, Centro Hospitalar do Porto, Portugal
Introduction: Systemic lupus erythematosus (SLE) patients have several
mechanisms by which they are more susceptible to common and
opportunistic infections. Immune responses to fungal antigens play
an important role in the host defense against dermatophytosis, especially microbicidal and growth inhibitory activity of neutrophils. These
immune pathways may be deregulated in SLE patients, either due to
broad-based immune dysfunction - genetic or acquired due to disease
itself (as dysfunction of B lymphocytes), or the use of immunosupressive therapies.
Case Description: Female 38 years old patient with longstanding SLE
with pulmonary hypertension (on dual vasodilator therapy), severe
hematological involvement (thrombocytopenia despite splenectomy
and severe neutropenia due to oligoclonal T cell proliferation) and
severe cutaneous involvement (patchy scalp alopecia with biopsy
proven acute lupus). She responded poorly to steroids and didnt
respond to cyclosporine. Granulocyte colony-stimulating factor and
rituximab were started, but ten days after the first infusion, she presented with scalp vesicular lesions and rapidly progression to sepsis
with periorbital and scalp cellulitis. Sepsis resolved with large-spectrum
antibiotics (carbapenem and vancomycin) and no bacterial agent was
identified. On a black light lamp, the alopecia lesions were fluorescent
and Microsporum canis was identified. After starting terbinafine, all
her hair grew in the next months. The neutropenia improved but the
thrombocytopenia remains 50.000/mcL.
Discussion: The presence of infection in autoimmune patients poses a
real challenge to the physician. In this patient a probably chronic quiescent dermatophytosis was unmasked by the addition of a strong and
new immunossupressive stimuli rituximab. It remains to be understood what the real fungal infection role was on SLE global activity
perpetuation before treatment.
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Lupus

Innate and adaptive immunity

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>> Version of Record - Mar 28, 2014

Lupus (2014) 23, 449499

9th European Lupus Meeting,

Innate and adaptive immunity

ANALYSIS OF CIRCULATING INTERFERON LEVELS IN

ACTIVATED T CELLS ENHANCE THE INTERFERON-a

Introduction: Interferon alpha (IFN-a) is a primary pathogenic factor

! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav

9th European Lupus Meeting

9th European Lupus Meeting

FOXP3 TREGS MODULATE DC AUTOPHAGY IN A

9th European Lupus Meeting

Aim: To dissect the molecular mechanism governing IFNa-induced

9th European Lupus Meeting

INCREASED EXPRESSION OF LOW DENSITY

JSLE clinical episodes

Mean change in phagocytosis was -11%, SD 12.46%

9th European Lupus Meeting

TREG CCR7-(% TREG)

9th European Lupus Meeting

THE IMPLICATION OF NETS ON THE UPREGULATION OF

THE INTERLEUKIN-6/INTRELEUKIN-6-RECEPTOR SYSTEM

Introduction: Monocyte chemoattractant protein-1 (MCP-1) has been

Introduction: Interleukin-6 (IL-6) is closely linked to CRP, but this

9th European Lupus Meeting

Genetics and -omics (genomics, metagenomics,

bp IRF5 CGGGG-indel was associated with a lower IFN-a

9th European Lupus Meeting

MICRO-RNA NETWORK ANALYSIS IN LUPUS NEPHRITIS

TRANS-ANCESTRAL IMMUNOCHIP STUDY TO UNRAVEL

9th European Lupus Meeting

Epidemiology and outcomes - Registries and

Patients and methods: In 2001 226 FDRs to a population-based lupus

ASSESSMENT OF DAMAGE ACCRUAL AND

9th European Lupus Meeting

Conclusions: Biopsy-proven lupus nephritis may be less common than

9th European Lupus Meeting

3 Stojanovich L, Zadman-Goddard G, Pavlovich S, Sikanich N.

9th European Lupus Meeting

9th European Lupus Meeting

9th European Lupus Meeting

American College of Rheumatology (ACR) criteria. The Years of

CVD; Cardiovascular disease, CNS; Central nervous system.

9th European Lupus Meeting

9th European Lupus Meeting

from secondary antiphospholipide syndrome after 10 and 14 yrs, and

9th European Lupus Meeting

Diagnostic, classification and outcome criteria

Recorded as of latest visit

9th European Lupus Meeting

9th European Lupus Meeting

OUTCOME OF ADULTS WITH CHILDHOOD ONSET

Forty three patients had completed secondary high school, 21 of them

9th European Lupus Meeting

Clinical features, diagnosis and co-morbidities

9th European Lupus Meeting

A REVIEW OF METABOLIC SYNDROME IN SYSTEMIC

ANALYSIS OF SPECTRAL DOMAIN OPTICAL COHERENCE

Aim: To investigate the prevalence of Metabolic syndrome (Mets) and

Potentially suitable n=261

Objective: Spectral domain Optical Coherence Tomography (SD-OCT)