Autoimmune Diseases and SLE Lecture Notes

Autoimmune Diseases

• Autoimmune diseases occur when the adaptive immune system attacks self-antigens, causing tissue damage due to a breakdown of self-tolerance.
• Nearly 4% of the world’s population is affected, with women being three times more likely to be affected than men.

Systemic Lupus Erythematosus (SLE)

• SLE is a systemic autoimmune disease characterized by a wide range of autoantibodies, especially antinuclear antibodies (ANAs).
• It is caused by immune complex deposition and antibody binding to various cells and tissues, affecting mainly the skin, joints, kidneys, and serosal membranes.
• Prevalence is about 400 per 100,000, particularly affecting women in their twenties or thirties (9:1 female-to-male ratio for ages 17-55).
• Higher incidence in blacks and Hispanics (2- to 3-fold higher) than in whites.

Pathogenesis of SLE

• Genetic Factors: Familial association, higher concordance in monozygotic twins (25%) compared to dizygotic twins (1-3%), HLA association (HLA-DR2 or HLA-DR3), and genetic deficiencies of classical pathway complement proteins.
• Environmental Factors: Exposure to UV light, sex hormones, and certain drugs (hydralazine, procainamide, D-penicillamine).
• Immunologic Factors: Failure of self-tolerance in B cells, CD4+ helper T cells escaping tolerance, Type I interferons, and TLR (Toll-like receptors) signals.

Autoantibodies in SLE

• Anti-Nuclear Antibodies (ANAs): Detected by indirect immunofluorescence.
• Antibodies to DNA, histones, nonhistone proteins bound to RNA, and nucleolar antigens.
• Anti-phospholipid antibodies directed against epitopes of plasma proteins in complex with phospholipids.
• Antibodies directed against blood cells

SLE Classification Criteria

• ANA titre of 1:80 or equivalent positive test.
• Fever (Temperature 38.3°C).
• Leucopenia (White blood cell count < 4.0 × 10^9/L).
• Thrombocytopenia (Platelet count < 100 × 10^9/L).
• Evidence of autoimmune haemolysis.
• Delirium, psychosis, or seizure.
• Non-scarring alopecia or oral ulcers.
• Subacute cutaneous or discoid lupus.
• Pleural or pericardial effusion or acute pericarditis.
• Joint involvement (synovitis or tenderness with morning stiffness).
• Proteinuria >0.5 g/24 hours.
• Class II or V lupus nephritis on renal biopsy.

Clinical and Pathologic Manifestations

• Common clinical manifestations include arthritis, arthralgia, myalgia, skin involvement, fever, fatigue, and weight loss.
• Renal involvement is significant (60%), along with neuropsychiatric (50-70%), pleuritis (25-35%), and pericarditis (45%) manifestations.
• Raynaud phenomenon (20%), ocular issues (15-40%), and peripheral neuropathy (5-15%) are also noted.

Morphology of SLE

• Blood Vessels: Acute necrotizing vasculitis with fibrinoid necrosis; chronic fibrous thickening with luminal narrowing.
• Skin: Butterfly rash, vacuolar degeneration of the basal layer, dermal edema, perivascular inflammation, and vasculitis.
• Cardiovascular System: Pericardial involvement (up to 50%), myocarditis, valvular endocarditis (Libman-Sacks), and coronary atherosclerosis.
• Spleen: Splenomegaly, capsular thickening, follicular hyperplasia, and onion-skin lesions (concentric hyperplasia of central penicilliary arteries).
• Central Nervous System: Microinfarcts, microthrombosis, vasculopathy, and rare vasculitis; immune-complex and complement activation.
• Joints: Nonerosive synovitis with little deformity.
• Lymph Nodes: Hyperplasia of B cell follicles.
• Lungs: Chronic interstitial fibrosis and pulmonary hypertension.

Lupus Nephritis

• Up to 50% of SLE patients have clinically significant renal involvement.
• Associated with immune complex deposition in the glomeruli.
• Six classes of glomerular disease:
  • Class I: Minimal mesangial lupus nephritis, immune complex deposition in the mesangium without structural changes.
  • Class II: Mesangial proliferative lupus nephritis, mesangial cell proliferation and matrix accumulation.
  • Class III: Focal lupus nephritis, involvement of fewer than 50% of glomeruli with segmental or global lesions.
  • Class IV: Diffuse lupus nephritis, most common type, affects half or more of the glomeruli.
  • Class V: Membranous lupus nephritis, diffuse thickening of capillary walls due to subepithelial immune complex deposition.
  • Class VI: Advanced sclerosing lupus nephritis, sclerosis of more than 90% of glomeruli, end-stage renal disease.