I. Molecular biology

  1. ANCA = antibodies directed against components of primary granules of neutrophils and lysosomes of monocytes
  2. Subtypes
    1. "Cytoplasmic" ANCA (c-ANCA)
      1. Directed against proteinase 3
      2. Highly specific and sensitive for active Wegener's Granulomatosis.
    2. "Perinuclear" ANCA (p-ANCA)
      1. Directed against myeloperoxidase
      2. More closely associated with microscopic polyangiitis, a smaller-vessel vasculitis; also Churg-Strauss syndrome
    3. "Atypical" ANCA
  3. T-cells appear to play a major role in ANCA-associated diseases

II. Etiology

  1. Genetic predisposition
  2. Exposure to silica
  3. Infections: TB, HIV, Hepatitis C, parvovirus B19
  4. Inflammatory bowel disease
  5. Neoplasia (lymphoma, myelodysplasia, monoclonal gammopathies)
  6. Drugs (propylthiouracil, cocaine, minocycline)
  7. Connective tissue diseases (lupus erythematosis, rheumatoid arthritis, dermatomyositis)

III. Clinical features

  1. Strongly associated with various Vasculitides (see above)
  2. May be involved in pauci-immune necrotizing glomerulonephritis
  3. ANCA titer is not tightly correlated with clinical severity of disease