This document discusses autoimmune diseases, which constitute 1-2% of the population. It defines pathologic autoimmunity and lists common organ-specific autoimmune diseases. The mechanisms of self-tolerance and its breakdown leading to autoimmunity are described. In-depth details provided on Systemic Lupus Erythematosus (SLE) include diagnostic criteria, associated autoantibodies, clinical features, pathology, and treatment approaches.

1. ‘Immune reactions against self-antigens’

2.  Pathologic autoimmunity: defined as
1. Presence of autoimmune reaction
2. Not secondary to tissue damage
3. Absence of other cause of disease
 Constitute 1-2% of population
AUTOIMMUNE DISEASES:

3. ORGAN-SPECIFIC:
 Hashimoto’s thyroiditis
 Autoimmune hemolytic an
 Good-Pauster syndrome
 Myasthenia Gravis
 Ulcerative colitis
 Primary Biliary cirrhosis
 SLE
 RA
 PAN
 Systemic sclerosis
 Sjögren syndrome
 Inflammatory myopathies

4. MECHANISM OF AUTOIMMUNITY

5.  Immune tolerance is Incapable of developing Immune response
to a specific antigen
 Self tolerance:::: is No immunological response towards self
antigens
 Self tolerance is necessary to avoid Autoimmunity
 Reduced self tolerance Autoimmune diseases
 Mechanism of self tolerance: Central / Peripheral

6. Self Reactive T - Lymphocytes
Anergy Suppression Apoptosis
Peripheral
Tolerance

7. Self Reactive
T - Lymphocytes
Genetic
Susceptibility
Inflammation
Tissue Injury
Tissue Damage

9. Systemic Lupus Erythematosus:
 “Multisystem disease of autoimmune origin,
characterized by a bewildering array of
autoantibodies, particularly antinuclear antibodies
(ANA’s)”.
 Chronic, remitting and relapsing, often febrile
illness characterized principally by injury to
skin, joints, kidney and serosal membranes.
 Predominantly disease of women, M:F=1:9

10. ? Autoimmune
Disease
? Type III
Hypersensitivity

12. 1997 revised criteria for SLE:
1. Renal disorder
2. Malar rash
3. Discoid rash
4. Serositis
5. Oral ulcer
6. Arthritis
7. Photosensitivity
8. Hematologic disorders
9. Immunology: Anti-ds DNA,
Anti-Sm, Antiphospholipid
10. Neurological disease
11. Antinuclear antibody
R-MD-SOAP-HINA
Presence of 4 or more out of these 11 criteria  SLE

14.  Directed against nuclear antigens
 4 Categories:
 Anti DNA,
 Anti Histones,
 Antibodies to non histone proteins,
 Antibodies to Nucleolar antigens
 Detection by Indirect Immunoflouresence
 Pattern of nuclear florescence suggests the type of Ab
ANTINUCLEAR ANTIBODIES

15. ANA- Anti Nuclear Antibodies
 ANA is positive in most of the Autoimmune disease
 In SLE, detection of ANA is a sensitive test but not specific
 APLA (Antiphospholipid antibody syndrome): seen in 40 to
50% of patients with SLE.

16. PATTERNS OF IMMUNOFLORESCENCE
Homogenous or Diffuse Antibodies to Chromatin,
Histones, Ds DNA
Rim or Peripheral staining Anti Ds DNA (40-60% SLE)
Speckled pattern Anti Sm, Ro, La (RNP)
Nucleolar pattern Systemic sclerosis patients
(Anti DNA Topo)

17. AUTOIMMUNE DISEASE SPECIFIC ANTIBODY
Systemic Lupus
Erythematosus
1. Anti Ds DNA
2. Anti Sm
Drug induced SLE Anti Histone
Systemic Sclerosis Anti DNA Topoisomerase I
(Scl 70)
Limited Scleroderma Anti Centromere
Sjogren Syndrome Anti SS-A (Ro)
Anti SS-B (La)
Inflammatory Myopathies Anti Jo1

18.  Morphology depends on nature of antibody, tissue involved,
course, duration of disease
 Deposition of immune complex **
 Acute necrotizing vasculitis
 Skin: Erythematous, Maculopapular eruption over malar
eminence-Classical feature.
SLE MORPHOLOGY

19. SLE- Multi-organ disease:
 Joint:
 Erosion of articular cartilage, swelling, inflammation
 CNS:
 Focal neurological deficits,
 Neuropsychiatric symptoms.
 Multifocal cerebral infarct.
 Heart:
 “Libman sacks endocarditis”.
 Pericarditis,
 Lung: Pleuritis, interstitial pneumonitis.

20.  “Lupus Nephritis”
 Most common cause of death—renal failure
 More of glomerular lesions are seen.
 Deposition of Immune complexes in Glomeruli
 25 to 30% of SLE kidneys appear normal on LM but 100%
involved when seen on IF, EM
RENAL LESIONS IN SLE

21.  Class I: Normal by LM, IF, EM
 Class II: Mesangial Glomerulonephritis
 Class III: Focal Glomerulonephritis
 Class IV: Diffuse proliferative Glomerulonephritis
 Class V: Membranous Glomerulonephritis
WHO CLASSIFICATION OF RENAL
LESIONS IN SLE

22.  Present in 40% - 50% of SLE
 Ab-directed against anionic plasma-proteins and plasma
protein epitopes.
 False positive test for syphilis as cardiolipin antibody used in
Syphilis reacts with these antibodies.
 Primary—not associated with SLE
 Secondary—associated with SLE.
ANTI-PHOSPHOLIPID AB:

23.  In Vivo: Thrombosis: Hypercoagulable status; THROMBOSIS–
by platelet activation, decreased PGI2 and protein C-
synthesis.
 In Vitro: Anticoagulant: interfere with clotting tests: like
APTT.

24.  Recurrent venous and arterial thrombosis– cardiac valvular
vegetations, deep venous ulcers, pulmonary
thromboembolism, pulmonary HT, stroke, bowel infarction
 Recurrent Fetal loss (antibody mediated inhibition of t-PA):
required for trophoblastic invasion of uterus.
Effect of Thrombosis:

25. Therapeutic Approaches of Autoimmune
Diseases
 Plasmapheresis
 Remove circulating antibodies
 Short term improvement
 Immunosuppression
 Steroids
 Cyclosporine A