{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:40:54Z","timestamp":1789926054531,"version":"4.0.1"},"reference-count":169,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013699","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft und Forschung","doi-asserted-by":"publisher","award":["01EC1901D"],"award-info":[{"award-number":["01EC1901D"]}],"id":[{"id":"10.13039\/501100013699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.<\/jats:p>","DOI":"10.3390\/ijms22126474","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T04:15:46Z","timestamp":1623903346000},"page":"6474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Granulomatous Inflammation in ANCA-Associated Vasculitis"],"prefix":"10.3390","volume":"22","author":[{"given":"Antje","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Institute of Anatomy & Experimental Morphology, University Hospital Hamburg-Eppendorf, University of Hamburg, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1841-7974","authenticated-orcid":false,"given":"Anja","family":"Kerstein-St\u00e4hle","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Comd\u00fchr","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0012-0163","authenticated-orcid":false,"given":"Sebastian","family":"Klapa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Institute of Experimental Medicine c\/o German Naval Medical Institute, Carl-Albrechts University of Kiel, 24119 Kronshagen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Institute of Anatomy & Experimental Morphology, University Hospital Hamburg-Eppendorf, University of Hamburg, 20251 Hamburg, Germany"},{"name":"Municipal Hospital Kiel, 24116 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"Holl-Ulrich","sequence":"additional","affiliation":[{"name":"Pathologie Hamburg, Labor Lademannbogen MVZ GmbH, 22339 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lamprecht","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"ref_1","first-page":"5","article-title":"2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"20","author":"Jennette","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kitching, A.R., Anders, H.J., Basu, N., Brouwer, E., Gordon, J., Jayne, D.R., Kullman, J., Lyons, P.A., Merkel, P.A., and Savage, C.O.S. 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