Autoimmune Diseases Dr. Raid Jastania

Autoimmune Diseases Group of diseases with common pathological process Presence of auto-antibody ?defect in B-cells or T-cells Genetic and Environmental etiological factors Result in failure of self-tolerance The process involve Ag-Ab binding and Ag-Ab complex formation Process may lead in complement activation and inflammation with tissue injury

Autoantibody Failure to maintain self-tolerance Autoantibody can be formed to: –Nuclear antigen –Cytoplasmic antigen –Cell surface antigen –Proteins and phospholipids

Anti Nuclear Antibody (ANA) ANA represent diversity of antibodies that bind to several nuclear antigen –Anti-DNA –Anti-Histone –Antibody to Non-Histone –Antibody to nucleolar antigen ANA is usually detected by indirect immunofluorescence

Anti Nuclear Antibody (ANA) Patterns of ANA staining: –Homogenous: antibody to chromatin, histone or DNA –Rim/Peripheral: antibody to DNA –Speckled: antibody to histone (Sm, ribonucleoprotein RNP, SS-A (Ro), SS-B (La)) –Nucleolar pattern

Systemic Lupus Erythematosus Autoimmune Disease Multi-system disease Variable behaviour, unpredictable, remitting relapsing, acute and gradual. May involve any organ Common: Skin, kidney, serosal membranes, joints, heart.

Systemic Lupus Erythematosus ANA (anti-DNA, anti-Sm, anti- phospholipid) Prevalence: 1/2500 person Female: male 9:1 1/700 women More common and severe in blacks (1/245) Onset: 2 nd or 3 rd decade

SLE: Criteria for Diagnosis Malar Rash Discoid Rash Photosensitivity Oral ulcers Arthritis Serositis Renal disorder Neurologic disorder Hematologic disorder Immunologic disorder ANA

SLE ANA is sensitive to SLE but not specific ANA is present in 5-15% of normal people More specific to SLE are” –Anti-DNA –Anti-Sm LE bodies (hematoxylin bodies) Antiphospholipid 40-50% of cases Antiphospholipid syndrome (lupus anticoagulants)

SLE Atiology Genetic factors –25% concordance in monozygotic twins –Increase risk of disease in family members –SLE and HLA-DQ association –Some SLE patients have deficiency in complement components

SLE Atiology Non-Genetic factors: –Lupus-like syndrome with drug admenistration, procainamide, hydralazine –Association with sex hormone (more in female) –Trigger by exposure to sun light

SLE Atiology Immunologic Factors: –Polyclonal B-cell activation? –Oligoclonal B-cell activation –CD4+ T helper cell activation

SLE: mechanism of tissue injury Immune complex disease –Example: deposition of Ag-Ab complex in glomeruli results in kidney disease Type II hypersensitivity: –Hemolysis –Thrombocytopenia

SLE: common clinical manifestations Hematologic: anemia, leukopenia, thrombocytopenia Arthritis Skin rash Fever Fatigue Weight loss Renal disease CNS abnormality Pleuritis Myalgia Pericarditis GI inflammation Raynaud phenomenon Peripheral neuropathy

Pathological Findings Ag-Ab complex deposition Common: kidney, hear, vessels, serosal membranes, and skin With the consequences of inflammation and tissue injury

Pathological Findings Vessels: –Acute necrotizing vasculitis Skin: –Rash, erythema –Cell injury/necrosis of the basal layer of epidermis, edema, inflammation –Deposition of Ig, complement components

Pathological Findings Joints –Inflammation of synuvium, edema, mononuclear cell infiltrate Spleen: –Enlargement with follicular hyperplasia Serosa: pleura, peritoneum, pericardium –Serous effusion –Fibrinous inflammation –fibrosis

Pathological Findings Heart: –Pericarditis, myocarditis –Valvular lesion: Libman-Sacks endocarditis –Coronary artery disease Kidney –Deposition of complexes in glomeruli –Lupus nephritis –Cell injury/necrosis, proliferation of mesangium, endothelium, and epithelium