Anti-Neutrophil Cytoplasmic Antibody (ANCA)

History

  • First described in early 1980’s

Physiology

  • Anti-Neutrophil Cytoplasmic Antibodies (ANCA): antibodies directed against neutrophil microbiocidal components, which are used in host defense
  • ANCA antibodies activate neutrophils, monocytes, and endothelial cells
  • Role of Infection in ANCA Development
    • ANCA has been found to be directed against various viral/bacterial/fungal/protozoal antgens, as well as endocarditis and cystic fibrosis
    • Chronic or recurent infection can result in exacerbation of pumonary vasculitis or relapse
    • Hypothesis: infections may give rise to ANCA through molecular mimicry

Types of ANCA

  • c-ANCA (cytoplasmic staining): typically directed against proteinase 3 (PR3)
    • Sensitivity: approximately 90-95% for systemic Wegener’s Granulomatosis, but only 65-85% in organ-limited Wegener’s Granulomatosis
  • p-ANCA (perinuclear staining): typically directed against myeloperoxidase (MPO)
    • Sensitivity/Specificity: generally considered poor sensitivity and specificity (as they can be found in multiple diseases)
  • x-ANCA: typically found in inflammatory bowel disease

Measurement of ANCA

  • ELISA
  • Indirect Immunofluorescence on ETOH-Fixed Neutrophils

Etiology of Elevated ANCA

  • Wegener’s Granulomatosis (see [[Wegeners Granulomatosis]]): c-ANCA
  • Churg-Strauss Syndrome (see [[Churg-Strauss Syndrome]]): p-ANCA
  • Microscopic Polyangiitis (see [[Microscopic Polyangiitis]]): p-ANCA
  • Pauci-Immune Glomerulonephritis (see [[Pauci-Immune Glomerulonephritis]]): p-ANCA
  • Isolated Pulmonary Capillaritis (see [[Isolated Pulmonary Capillaritis]]): p-ANCA
  • Polyarteritis Nodosa (see [[Polyarteritis Nodosa]]): p-ANCA
  • Rheumatoid Arthritis (see [[Rheumatoid Arthritis]]):: p-ANCA
  • Goodpasture’s Syndrome (see [[Goodpastures Syndrome]]): p-ANCA
  • Drugs
    • All-Trans Retinoic Acid (see [[All-Trans Retinoic Acid]])
    • Phenytoin (see [[Phenytoin]])
    • Propylthiouracil (see [[Propylthiouracil]])
    • Mitomycin (see [[Mitomycin]])

Relationship of ANCA to Disease Activity

  • ANCA titers do not correlate with disease activity or predict relapse