Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Aug;10(8):463-73.
doi: 10.1038/nrrheum.2014.103. Epub 2014 Jul 8.

Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease

J Charles Jennette  1 , Ronald J Falk  1
Affiliations
Review

Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease

J Charles Jennette et al. Nat Rev Rheumatol. 2014 Aug.

Abstract

Antineutrophil cytoplasmic autoantibodies (ANCAs) are the probable cause of a distinct form of vasculitis that can be accompanied by necrotizing granulomatosis. Clinical and experimental evidence supports a pathogenesis that is driven by ANCA-induced activation of neutrophils and monocytes, producing destructive necrotizing vascular and extravascular inflammation. Pathogenic ANCAs can originate from precursor natural autoantibodies. Pathogenic transformation might be initiated by commensal or pathogenic microbes, legal or illegal drugs, exogenous or endogenous autoantigen complementary peptides, or dysregulated autoantigen expression. The ANCA autoimmune response is facilitated by insufficient T-cell and B-cell regulation. A putative pathogenic mechanism for vascular inflammation begins with ANCA-induced activation of primed neutrophils and monocytes leading to activation of the alternative complement pathway, which sets in motion an inflammatory amplification loop in the vessel wall that attracts and activates neutrophils with resultant respiratory burst, degranulation, extrusion of neutrophil extracellular traps, apoptosis and necrosis. The pathogenesis of extravascular granulomatosis is less clear, but a feasible scenario proposes that a prodromal infectious or allergic condition positions primed neutrophils in extravascular tissue in which they can be activated by ANCAs in interstitial fluid to produce extravascular necrotizing injury that would initiate an innate granulomatous inflammatory response to wall off the necrotic debris.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kidney Int. 2004 Oct;66(4):1535-40 - PubMed
    1. Ann Rheum Dis. 1999 Apr;58(4):237-45 - PubMed
    1. Kidney Int. 2010 Sep;78(6):590-7 - PubMed
    1. J Clin Invest. 1997 Sep 15;100(6):1416-24 - PubMed
    1. Kidney Int. 1992 Feb;41(2):375-83 - PubMed

Publication types