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Autoimmune

Diseases

Immune system :
Distinguish foreign antigens
from self component of body
tissues.
Autoimmune response : Activating
lymphocyte and producing
autoantibody against selfantigens.

Define pathologic autoimmunity


needs 3 requirements
Presence of an autoimmune
reaction
NOT secondary to tissue
damage, e.g. from infection
Absence of another welldefined cause of disease

Autoimmune disease :
result from tissue injury
cause by T-cell or antibodies
that react against selfantigens

Classification of Autoimmune
diseases
1.Tissue or organ specific disease
Autoantibody against a single
organ or tissue

2.Generalized or systemic disease


Autoantibody against widespread
antigens

Systemic Lupus
Erythematosus
(SLE )

Chronic systemic
autoimmune disease
characterized by loss of
self-tolerance and
production of
autoantibodies

Symptoms: Fever, weight loss,


hair loss, mouth and nose sore
9%
joint inflammation
50% Butterfly rash on the
nose and cheeks
20% Reynaud'sphenomenon

Diagnostic Criteria for SLE : 4/11

1. MALAR RASH

2. DISCOID RASH

3. PHOTOSENSITIVITY SKIN
RASH

4.ORAL OR NASOPHARYNGEAL
ULCERATION

5. SEROSITIS. PLEURITIS OR
PERICARDITIS

6. NON-EROSIVE ARTHRITIS

7. RENAL DISORDER
Persistant proteinuria
>0.5 g/day OR
>3+ OR
Cellular castes

8.
NEUROLOGICAL
DISORDER
SEIZURES OR
PSYCHOSIS

9. HEMATOLOGICAL DISORDER
Hemolytic anemia (AIHA)
Leukopenia <4000/mm3, on 2 or
more occasions
Lymphopenia <1500/mm3, on 2 or
more occasions
Thrombocytopenia <100000/mm3

10. IMMUNOLOGIC DISORDER


POSITIVE LE Preparation,Anti dsDNA,
Anti Sm
OR
FALSE POSITIVE test for syphilis at
least 6 months, confirmed by
Treponemal Pallidum Immobilization or
Fluorescent Treponemal antibody
absorption test

11. ANTINUCLEAR ANTIBODY

Etiology and Pathogenesis :


Female : Male = 9:1
Type 2 & 3 hypersensitivity
B-cell activation and
production of antinuclear
autoantibodies (ANAS)
against DNA, histone protein,
nonhistone protein, nucleolar
antigens

Laboratory tests for the


diagnosis of SLE :

ANAs
indirect immunofluorescence
positive in >95% patient with SLE
but it is not specific
Anti double-stranded DNA (40-60%)
and Anti Smith (Sm) (20-30%)
High specificity in diagnosis of SLE

LE cell test
positive ~80% of SLE
LE cell is any phagocytic
(neutrophil or macrophage)
phagocytize round
hamatoxylin bodies
Found in pleural or synovial fluid
or in tissue section

LE cell

Pathological Abnormallities in
SLE
Kidney :
immune complex deposit
in renal structure
increase thickness and
rigidity of the GBM of
peripheral capillary loops
"wire loops" are common

Wire
loop

Mesangial and peritubular granular deposits


of C1Q in a patient with diffuse proliferative
lupus nephritis

Granular peritubular deposits


of IgG

Skin :
Liquefactive degeneration
(vacuolization) of the basal layer
of the epidermis
Edema and perivascular
mononuclear in dermis
Deposition of immunoglobulin
along the dermal-epidermal
junction

Pericarditis and other serosal


cavity involvement :

Pericarditis
Nonbacterial endocarditis
(Libman-Sacks endocarditis)
cause by vegetations
affected to the valve leaflet
Mesangial become thickened
obliterate serosal cavity

Spleen :
Capsular thickening
Follicular hyperplasia
Thickening and perivascular
fibrosis Onion-skin
appearance
is pathognomonic

Sjogrens
syndrome

An autoimmune disease
characterized by destruction
of the lacrimal and salivary
glands
Result in dry eyes
(keratoconjunctivitis sicca)
and dry mouth (xerostomia)
Including respiratory and
gastrointestinal tracts

Primary form (isolated


disorder) = sicca syndrome
Secondary form such as
rheumatoid arthritis, SLE,
scleroderma, polymyositis,
thyroiditis
Increase risk lymphoma

Pathogenesis
Anti ribonucleoprotein Ab
Anti SSA (Ro)
Anti SSB (La)

Decrease in tears and saliva


is the result of lymphocytic
infiltration and fibrosis of
the lacrimal and salivary
gland

Perivascular lymphocytic
infiltration
Enlargement of salivary &
lacrimal glands (Mikulicz
syndrome)
Ductal epithelial
hyperplasia

Athrophy of the acini,


fibrosis, hyalinization
Biopsy of the lip (to
examine minor salivary
gland) is essential for the
diagnosis of Sjogrens
syndrome

Systemic
sclerosis
(scleroderma)

An autoimmune disease
characterized by fibroblast
stimulation and deposition
of collagen in skin and
internal organs

Classified
disease

1. Systemic sclerosis
- Widespread skin involvement
- Early internal organs involvement
- Anti DNA topoisomerase1 Ab (Scl-70)

2. Localized scleroderma
- skin involvement of face and hands
- Late internal organs involvement
- Anti centromere Ab

Diagnostic Criteria for SSc :


1 major OR 2 minor
MAJOR CRITERION:
PROXIMAL SCLERODERMA
Thickening of the skin proximal
to the metacarpophalangeal or
metatarsophalangeal joints

MINOR CRITERIA:
1. SCLERODACTYLY:
Skin changes limited to the fingers

2. BASILAR PULMONARY FIBROSIS

3.DIGITAL PITTING SCARS OR


LOSS OF SUBSTANCE OF THE
FINGER PAD

Etiology and Pathogenesis


Unknown
likely a combination of
abnormal immune responses
resulting in accumulation of
growth factors
(IL1,PDGF,FGF) that act on
fibroblasts and stimulate
collagen production

Pathological Abnormality in
Scleroderma
Skin :
Early stages
Skin have a doughy
consistency
perivascular infiltrates
containing CD4+T cells

swelling and
degeneration of collagen
fibers
Thickening of basal
laminar, endothelial cell
-damage and partial
occlusion of capillaries
and small arteries

DOUGHY SKIN

FISH MOUTH

Edematous phase
Progressive fibrosis of
dermis
Increase of compact
collagen in dermis
Thinning of epidermis
Atrophy of dermal
appendages

Hyaline thickening of
walls of dermal
arterioles & capillaries
Patient with CREST may
have diffuse
subcutaneous
calcification

Advanced stages
Clawlike appearance
of fingers
Loss of blood supply
may lead to cutaneous
ulceration & atrophic
changes in the
terminal phalanges

Ulcer at the finger tip (rat bite


necrosis )

Salt & Pepper appearance

Alimentary tract :
Progressive atrophy and
collagenous fibrous
replacemant of muscle
Lower 2/3 of esophagus
develops a rubber-hose
inflexibility

Lungs :
Pulmonary hypertension
& interstitial fibrosis
Pulmonary hypertension
(vascular changes,
pulmonary vasospasm)

Scleroderma lung

Scleroderma lung fibrosis

Rheumatoid
Arthritis

Chronic inflammatory
disease affects primarily
the joints, may involve
extra-articular tissue
Associated with anti-IgG
autoantibodies called
rheumatoid factors

Pathogenesis
Proliferative changes in the
synovial membrane
infiltrated with
lymphocytes, plasma cell
and macrophages
Destructive erosion of joint
cartilage and bone cartilage
Joint space become
obliterated

Diagnostic Criteria for RA : 4/7


1. MORNING STIFFNESS
at least 1 hr. for at least 6
wks.
2. SWELLING OF THREE OR
MORE JOINTS
for at least 6 wks.

3. SWELLING OF
WRIST,MCP OR PIP
for at least 6 wks.
4. SYMMETRICAL JOINT
SWELLING.
for at least 6 wks.

5. HAND XRAY CHANGES


TYPICAL OF RA

6. SERUM RHEUMATOID
FACTOR POSITIVE

7. RHEUMATOID NODULES

Inflammatory
Myopathies

Injury & inflammation of


mainly the skeletal
muscles
Three distinct disorders
dermatomyositis
polymyositis
inclusion-body myositis

Heliotro
ph

Grottons sign

Polymyosit
is

THE END