Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

Annu Rev Pathol. 2013 Jan 24;8:139-60. doi: 10.1146/annurev-pathol-011811-132453.

Abstract

Clinical, in vitro, and experimental animal observations indicate that antineutrophil cytoplasmic autoantibodies (ANCA) are pathogenic. The genesis of the ANCA autoimmune response is a multifactorial process that includes genetic predisposition, environmental adjuvant factors, an initiating antigen, and failure of T cell regulation. ANCA activate primed neutrophils (and monocytes) by binding to certain antigens expressed on the surface of neutrophils in specific inflammatory microenvironments. ANCA-activated neutrophils activate the alternative complement pathway, establishing an inflammatory amplification loop. The acute injury elicits an innate inflammatory response that recruits monocytes and T lymphocytes, which replace the neutrophils that have undergone karyorrhexis during acute inflammation. Extravascular granulomatous inflammation may be initiated by ANCA-induced activation of extravascular neutrophils, causing tissue necrosis and fibrin formation, which would elicit an influx of monocytes that transform into macrophages and multinucleated giant cells. Over time, the neutrophil-rich acute necrotizing lesions cause the accumulation of more lymphocytes, monocytes, and macrophages and produce typical granulomatous inflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / pathology*
  • Autoantibodies / immunology*
  • Humans
  • Macrophages / immunology
  • Macrophages / pathology
  • Neutrophils / immunology
  • Neutrophils / pathology

Substances

  • Autoantibodies