Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis.
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.
Department of Pathology and Laboratory Medicine, and UNC Kidney Center, University of North Carolina, Chapel Hill, NC 27599, USA. jcj@med.unc.edu
J Charles
JC
Jennette
Ronald J
RJ
Falk
Peiqi
P
Hu
Hong
H
Xiao
D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies