{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:55:22Z","timestamp":1791960922928,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2004,8,25]],"date-time":"2004-08-25T00:00:00Z","timestamp":1093392000000},"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":[[2004,8,31]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>A characteristic feature of Wegener's granulomatosis is the presence of antineutrophil cytoplasm antibodies (ANCA) to proteinase 3 (PR3). In vitro, ANCA activate neutrophils by co-ligating PR3 and Fc\u03b3RIIa\/IIIb receptors. ANCA are predominantly of the IgG isotype, and IgG1, IgG3 and IgG4 subclasses are particularly represented. To address the pathogenic role of individual ANCA-IgG subclass antibodies, patients\u2019 sera were screened using indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and subclass PR3-ELISA to identify patients with high titres of PR3-ANCA within the IgG1, IgG3 or IgG4 subclasses. Unfractionated ANCA-IgG and subclass fractions were isolated by affinity chromatography and compared for their capacities to stimulate superoxide production by primed human neutrophils. Donor neutrophils were analysed for constitutive and induced Fc\u03b3RI expression by flow cytometry. The IgG1, IgG3 and IgG4 subclass fractions, isolated from three different ANCA sera, each stimulated superoxide production from neutrophils derived from multiple donors. Subsequently, IgG4 subclass fractions isolated from a further four ANCA positive sera demonstrated varying abilities to stimulate release of superoxide; unrelated to PR3-ANCA titre, neutrophil donor, or neutrophil Fc\u03b3RI expression. The stimulation of superoxide release by IgG1- and IgG3-ANCA subclass fractions is consistent with the proposed mechanism of co-ligation of PR3 antigen and Fc\u03b3RIIa\/IIIb receptors. However, the demonstration of similar activity for the IgG4-ANCA subclass fractions isolated from some sera was unexpected. This activity was independent of neutrophil donor and expression of Fc\u03b3RI, suggesting it was capable of activating neutrophils via constitutively expressed Fc\u03b3RIIa\/IIIb or co-ligation of other, unidentified, cell surface molecules.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02566.x","type":"journal-article","created":{"date-parts":[[2004,9,16]],"date-time":"2004-09-16T13:49:46Z","timestamp":1095342586000},"page":"183-192","source":"Crossref","is-referenced-by-count":83,"title":["Anti-neutrophil cytoplasm antibody IgG subclasses in Wegener's granulomatosis: a possible pathogenic role for the IgG4 subclass"],"prefix":"10.1093","volume":"138","author":[{"given":"M","family":"HOLLAND","sequence":"first","affiliation":[{"name":"MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"HEWINS","sequence":"additional","affiliation":[{"name":"MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham"},{"name":"Department of Nephrology, University Hospital Birmingham NHS Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"GOODALL","sequence":"additional","affiliation":[{"name":"MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"ADU","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Birmingham NHS Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"JEFFERIS","sequence":"additional","affiliation":[{"name":"MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C O S","family":"SAVAGE","sequence":"additional","affiliation":[{"name":"MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,8,25]]},"reference":[{"key":"2022010901424851100_b1","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1046\/j.1523-1755.2001.00962.x","article-title":"Nephrology forum. 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