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Recent disease definitions and classification criteria allow distinction between granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and non-granulomatous microscopic polyangiitis (MPA). The discovery of ANCA\u2014autoantibodies directed against proteolytic enzymes of neutrophil granules\u2014has enabled earlier diagnosis of AAV and paved the way to stage-adapted treatments. ANCA testing initially relied on different immunofluorescence patterns, i.e., cytoplasmic ANCA (C-ANCA) vs. perinuclear ANCA (P-ANCA), in ethanol-fixed neutrophils. This is nowadays outperformed by well-standardized immunoassays against the ANCA target antigens proteinase\u00a03 (PR3) and myeloperoxidase (MPO) for the diagnosis of small-vessel vasculitides. The discovery of ANCA has contributed substantially to unravelling the pathogenesis of AAV, which comprises neutrophil degranulation, NETosis with concurrently amplified ANCA antigen presentation, and intra- and transmural vascular inflammation involving the alternative complement system in susceptible individuals. There is a\u00a0genetic disposition concerning certain HLA alleles and polymorphisms of the proteinase\u00a03 gene. Furthermore, epigenetic modifications impact on disease activity and relapse. During follow-up, the ANCA titer is not a\u00a0reliable mirror of disease activity; however, PR3-ANCA positivity is associated with a\u00a0greater likelihood of relapse and a\u00a0better treatment response to rituximab as compared to cyclophosphamide\/azathioprine. Within the past 60\u00a0years, the discovery of ANCA has revolutionized the ability to diagnose, understand, classify, and treat AAV in a\u00a0targeted manner.<\/jats:p>","DOI":"10.1007\/s00393-024-01599-4","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T20:27:47Z","timestamp":1733862467000},"page":"219-224","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["History of antineutrophil cytoplasmic autoantibodies","Geschichte der antineutrophilen zytoplasmatischen Autoantik\u00f6rper"],"prefix":"10.1007","volume":"84","author":[{"given":"Kirsten","family":"de Groot","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Csernok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"van der Woude","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"issue":"11","key":"1599_CR1","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1172\/JCI103987","volume":"38","author":"P Calabresi","year":"1959","unstructured":"Calabresi\u00a0P, Edwards\u00a0EA, Schilling\u00a0RF (1959) Fluorescent antiglobulin studies in leukopenic and related disorders. 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E.\u00a0Csernok, and D.\u00a0van der Woude declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}