{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:38:57Z","timestamp":1790894337826,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T00:00:00Z","timestamp":1486425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Anti-neutrophil cytoplasmic antibodies (ANCA) appear to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). However, ANCA alone are not sufficient to generate disease, and some evidence suggests that infectious triggers may serve as inciting events for AAV disease activity. Antibodies of the immunoglobulin (Ig)M isotype often serve as markers of recent infection, and IgM ANCA have been identified previously in patients with AAV, although the frequency and clinical relevance of IgM ANCA is not well established. We sought to characterize IgM ANCA more clearly by creating a novel enzyme-linked immunosorbent assay (ELISA) for IgM antibodies to proteinase 3 [IgM proteinase 3 (PR3)\u2013ANCA], which we applied to two large, clinically well-characterized trial cohorts of patients with granulomatosis with polyangiitis and microscopic polyangiitis. In the first cohort, IgM PR3\u2013ANCA occurred with a frequency of 15\u00b70%, and were associated with a higher degree of disease severity and a trend towards a higher rate of alveolar haemorrhage (29\u00b76 versus 15\u00b77%, P\u2009=\u20090\u00b710). Analysis of follow-up samples in this cohort showed that the presence of IgM PR3\u2013ANCA was transient, but could recur. In the second cohort, IgM PR3\u2013ANCA occurred with a frequency of 41\u00b71%, and were also associated with a higher degree of disease severity. A higher rate of alveolar haemorrhage was observed among those with IgM PR3\u2013ANCA (45\u00b73 versus 15\u00b78%; P\u2009&amp;lt;\u20090\u00b7001). The association of transient IgM PR3\u2013ANCA with an acute respiratory manifestation of AAV suggests a possible link between an infectious trigger and AAV disease activity.<\/jats:p>","DOI":"10.1111\/cei.12925","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T23:21:02Z","timestamp":1484176862000},"page":"174-181","source":"Crossref","is-referenced-by-count":13,"title":["Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis"],"prefix":"10.1093","volume":"188","author":[{"given":"J M","family":"Clain","sequence":"first","affiliation":[{"name":"Mayo Clinic and Foundation, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Hummel","sequence":"additional","affiliation":[{"name":"Mayo Clinic and Foundation, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J H","family":"Stone","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F C","family":"Fervenza","sequence":"additional","affiliation":[{"name":"Mayo Clinic and Foundation, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G S","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C G M","family":"Kallenberg","sequence":"additional","affiliation":[{"name":"University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Langford","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W J","family":"McCune","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P A","family":"Merkel","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P A","family":"Monach","sequence":"additional","affiliation":[{"name":"Boston University Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Seo","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R F","family":"Spiera","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E W","family":"St Clair","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S R","family":"Ytterberg","sequence":"additional","affiliation":[{"name":"Mayo Clinic and Foundation, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Specks","sequence":"additional","affiliation":[{"name":"Mayo Clinic and Foundation, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,7]]},"reference":[{"key":"2021120808031740400_cei12925-bib-0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum"},{"key":"2021120808031740400_cei12925-bib-0002","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.amjmed.2004.02.030","article-title":"The antineutrophil 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