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: 2nd or 3rd 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