Research letter
Gene expression profiling of skin and blood in
hidradenitis suppurativa
DOI: 10.1111/bjd.14371
DEAR EDITOR, Hidradenitis suppurativa (HS) is characterized
by recurrent abscesses, nodules and sinus tract formation
and is localized mainly in the body folds. The pathogenesis
is poorly understood. Mutations in genes encoding essential
compounds of the transmembrane protease c-secretase,
including NCSTN, PSEN1 and PSENEN, have been identified in
familial HS.1,2 These mutations may result in impaired
Notch signalling, promoting cyst formation and continuing
inflammatory activity.3 Additionally, certain single-nucleotide
polymorphisms at the promoter region of the tumour
necrosis factor (TNF)-a gene were found to be associated
with HS.4 Furthermore, elevated levels of interleukin (IL)-1,
TNF-a and IL-10 were demonstrated in both lesional and
perilesional skin of patients with HS,5 and increased expres-
sion of the IL-23/T helper 17 pathway was found in
lesional skin.6 A recent study demonstrated that the produc-
tion of proinflammatory cytokines in HS is compartmental-
ized, as the levels were elevated in pus collected from
lesional skin but suppressed in circulating blood mononu-
clear cells.7
To acquire a better understanding of the molecular patho-
genesis of HS, we performed mRNA microarray studies to
compare gene expression in lesional skin vs. healthy skin of
patients with HS. Also, the gene expression profiles in whole
blood of patients and unaffected individuals were determined.
The study was approved by the university medical ethics com-
mittee.
Seventeen patients with HS were included. Whole blood
was collected from all patients and 10 healthy controls. Skin
biopsies of 3 mm were obtained from inflammatory lesions in
all 17 subjects. Additionally, an extra biopsy from clinically
healthy skin of the upper arm or leg was obtained from 13 of
these 17 individuals. The skin samples were immediately fro-
zen in liquid nitrogen and subsequently stored at 80 C.
mRNA was extracted from skin samples using the Qiagen
RNeasy Fibrous Tissue Mini Kit (Qiagen Inc., Valencia, CA,
U.S.A.) and from whole blood with the Qiagen PAXgene
Blood RNA Kit according to the manufacturers instructions.
RNA was hybridized to the GeneChip HT HG-U133+PM Array
(Affymetrix, Santa Clara, CA, U.S.A.). The raw data have been
deposited in the National Center for Biotechnology Informa-
tions Gene Expression Omnibus under accession number
1392 British Journal of Dermatology (2016) 174, pp13921394
GSE72702. Pathway analyses were conducted with Qiagens
Ingenuity Pathway Analysis. Array Studio software version 8.0
(OmicSoft Corp., St Morrisville, NC, U.S.A.) was used to anal-
yse microarray data. Dysregulated genes were identified using
a general linear model with multiple testing correction.
Expression modulation with a fold change > 2 or < 2 and a
false-discovery-rate-adjusted P-value < 0
05 were considered
significant.
A significant difference was observed in mRNA expression
between lesional and clinically healthy skin of patients with
HS, with 1145 probe sets representing over 800 genes having
at least a twofold change (P < 0
05) (Table S1; see Supporting
Information). Patients with the most dysregulated gene pro-
files were more likely to have long-standing disease
(> 15 years) (Fig. 1a). Pathway analyses of the modulated
genes showed that they were related mostly to inflammation,
including cell adhesion, diapedesis and extravasation, as well
as immune cell signalling and communication pathways
(Fig. 1b; Table S2; see Supporting Information). An interest-
ing finding is involvement of the atherosclerosis signalling
pathway in lesional HS skin, as it supports the current thought
that the inflammatory response in HS is associated with meta-
bolic syndrome.8
Expression of NCSTN, PSEN1 and PSENEN was not modu-
lated in lesional vs. clinically healthy skin of patients. No sig-
nificant differences were identified in whole-blood mRNA
expression between patients (n = 17) and healthy controls
(n = 10) (Fig. S1; see Supporting Information). Nonetheless,
the top 50 probe set that were differentially expressed based
on raw P-value are provided in Table S3 (see Supporting
Information). The lack of differences between patients with
HS and healthy controls in whole blood supports the
hypothesis of Kanni et al.,7 proposing that decreased cytokine
production in the blood circulation of patients with HS is
regulated at a post-transcriptional level. The authors suggest
that elevated TNF-a levels in serum of patients with HS, as
previously demonstrated by Matusiak et al.,9 may have a role
in this decreased production, as the number of mononuclear
cells was shown to be equal to or even greater than the
number in healthy controls.
In summary, we have demonstrated significantly altered
gene expression in lesional skin compared with clinically
healthy skin of patients with HS. This, in addition to the find-
ing that whole-blood RNA expression did not differ between
patients with HS and healthy subjects, indicates that activated
cells in HS reside in affected tissue. This may be due to activa-
tion and migration of leucocytes from the circulation into skin
2015 British Association of Dermatologists
 Research letter 1393

(a)

(b)

Fig 1. Gene expression profile in hidradenitis suppurativa (HS) skin. (a) The heat map of differentially expressed genes in HS skin based on
mRNA microarray analysis. A significant difference was observed in mRNA expression between lesional (grey boxes) and nonlesional patient skin
(red boxes). Patients with the most dysregulated gene profiles were more likely to have long-standing disease. (b) The top 10 canonical pathways
involved in the disease profile of patient skin.

tissue in response to released inflammatory chemokines. How- gene expression between clinically healthy skin from predilec-
ever, our results must be interpreted with caution, as the tion sites of patients with HS and skin of unaffected individu-
sample size was relatively small. Additionally, reverse- als from the same sites would be an interesting additional
transcriptase polymerase chain reaction techniques or study.
immunohistochemical analyses were not performed to confirm
1
our findings. As perilesional skin of patients with HS already Department of Dermatology, University J.L. BLOK1
shows histological abnormalities,10 one may hypothesize that Medical Center Groningen, University of K. LI2
the skin type of patients with HS in general is genetically dif- Groningen, Groningen, the Netherlands C. BRODMERKEL2
2
ferent from that of normal human skin, making patients prone Janssen Research & Development, LLC, M.F. JONKMAN1
to the development of HS lesions under certain mechanical Spring House, PA, U.S.A. B . H O R V AT H 1
and lifestyle triggers. Therefore, investigating differences in E-mail: j.l.dickinson-blok@umcg.nl

2015 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp13921394
1394 Research letter

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British Journal of Dermatology (2016) 174, pp13921394 2015 British Association of Dermatologists