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SLE Overview and Pathogenesis

Jun 29, 2025

Overview

This lecture explains systemic lupus erythematosus (SLE), a systemic autoimmune disease affecting multiple organs, its causes, diagnostic criteria, and management.

Definition and Pathogenesis

  • Systemic lupus erythematosus (SLE) is a systemic autoimmune disease causing inflammation in various organs.
  • "Systemic" means affecting multiple organs; "erythematosus" refers to skin redness; "lupus" refers to wolf, due to skin lesion appearance.
  • SLE occurs when immune cells attack the body's own tissues (autoimmunity).
  • Both genetic susceptibility and environmental triggers (e.g., UV light) contribute to SLE development.
  • UV radiation can cause cell damage and apoptosis, exposing nuclear antigens to the immune system.
  • People with certain genes have poor clearance of apoptotic bodies and produce antinuclear antibodies (ANA).
  • Antinuclear antibodies bind nuclear antigens, forming complexes that deposit in tissues and cause inflammation (type III hypersensitivity).
  • Other triggers include smoking, infections, certain drugs, and hormones like estrogen.
  • SLE is much more common in women, especially during reproductive years.

Symptoms and Diagnostic Criteria

  • Classic symptoms: fever, joint pain, and rash, especially in women of childbearing age.
  • Diagnosis requires at least 4 of 11 criteria:
    • Malar (butterfly) rash over cheeks.
    • Discoid rash—chronic, patchy redness, may scar.
    • Photosensitivity—rashes on sun-exposed skin.
    • Oral or nasal mucosal ulcers.
    • Serositis—inflammation around lungs (pleuritis) or heart (pericarditis).
    • Arthritis—pain in two or more joints.
    • Renal disorders, e.g., proteinuria or glomerulonephritis.
    • Neurologic disorders—seizures or psychosis.
    • Hematologic disorders—anemia, leukopenia, or thrombocytopenia.
    • Presence of antinuclear antibodies (ANA).
    • Other specific autoantibodies (anti-Smith, anti-dsDNA, antiphospholipid).

Antibodies and Complications

  • Anti-Smith and anti-dsDNA antibodies are more specific for SLE.
  • Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-beta2 glycoprotein I) can cause antiphospholipid syndrome, increasing clot risk.
  • SLE features both type III (immune complex mediated) and type II (antibody mediated) hypersensitivity reactions.

Treatment and Management

  • SLE has periods of flare-ups and remission.
  • Management aims to prevent flares (sun protection) and reduce inflammation (corticosteroids/immunosuppressants).
  • Severe cases may require long-term anticoagulation for clot prevention.

Key Terms & Definitions

  • Systemic lupus erythematosus (SLE) — An autoimmune disease affecting multiple organs.
  • Autoimmune disease — The immune system attacks the body’s own tissues.
  • Antinuclear antibody (ANA) — Antibody attacking nuclear components; present in SLE.
  • Type III hypersensitivity — Tissue damage from immune complex deposition.
  • Type II hypersensitivity — Tissue damage from antibodies targeting specific cells.
  • Antiphospholipid syndrome — Clotting disorder caused by antiphospholipid antibodies.
  • Photosensitivity — Skin reaction following sun exposure.

Action Items / Next Steps

  • Review the 11 diagnostic criteria for SLE.
  • Study the differences between type II and type III hypersensitivity reactions.
  • Read about common SLE treatments and their mechanisms.