{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:21:33Z","timestamp":1778862093259,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine concentrations of circulating antibodies targeting C3a and C5a complement receptors in antineutrophil cytoplasmic autoantibody (ANCA)\u2013associated vasculitis (AAV) and analyze their association with disease activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Concentrations of antibodies against C3a and C5a complement receptors (anti\u2010C3aR and anti\u2010C5aR) and plasma complement fragments C3a and C5a were determined in patients with AAV (n\u00a0=\u00a0110; granulomatosis with polyangiitis [GPA; n\u00a0=\u00a082] or microscopic polyangiitis [MPA; n\u00a0=\u00a028]), systemic lupus erythematosus (SLE) patients as disease controls (n\u00a0=\u00a036), and healthy donors (n\u00a0=\u00a0220). C3aR and C5aR expression by circulating neutrophils, monocytes, and T cells was analyzed using flow cytometry. Clinical data were assessed at time of serum sampling and during follow\u2010up for 60 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In AAV, anti\u2010C3aR and anti\u2010C5aR antibodies were decreased (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0026 and <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.0001, respectively). In remission, anti\u2010C3aR antibody concentrations rose to values comparable to healthy donors, whereas anti\u2010C5aR antibody concentrations did not. In GPA, anti\u2010C5a and anti\u2010C5aR antibody concentrations inversely correlated with each other (r\u00a0=\u00a0\u22120.6831, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0127). In newly diagnosed GPA, decreased concentrations of anti\u2010C5aR antibodies but not anti\u2010C3aR antibodies were associated with disease activity (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0009). Moreover, low anti\u2010C5aR antibodies were associated with relapse in GPA (hazard ratio 3.54, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0009) and MPA (hazard ratio 4.41, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0041). The frequency of C5aR\u2010expressing cells within T cell populations was increased in GPA (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0021 for CD4+ T cells; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0118 for CD8+ T cells), but not in MPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Low concentrations of anti\u2010C5aR antibodies reflect disease activity and are associated with an increased risk for relapse in AAV.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42410-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42410","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T12:18:13Z","timestamp":1669033093000},"page":"760-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Low Concentrations of C5a Complement Receptor Antibodies Are Linked to Disease Activity and Relapse in Antineutrophil Cytoplasmic Autoantibody\u2013Associated Vasculitis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0012-0163","authenticated-orcid":false,"given":"Sebastian","family":"Klapa","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of L\u00fcbeck, L\u00fcbeck, Germany, and Institute of Experimental Medicine Christian\u2010Albrecht University of Kiel c\/o German Naval Medical Institute  Kronshagen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Koch","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Christian\u2010Albrecht University of Kiel c\/o German Naval Medical Institute  Kronshagen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Kerstein\u2010St\u00e4hle","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"K\u00e4hler","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Christian\u2010Albrecht University of Kiel c\/o German Naval Medical Institute  Kronshagen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Heidecke","sequence":"additional","affiliation":[{"name":"CellTrend GmbH  Luckenwalde Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Schinke","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Huber\u2010Lang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Trauma\u2010, Hand\u2010, Plastic\u2010 and Reconstruction Surgery University of Ulm  Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Nitschke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Transplant Center University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Pitann","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solveig","family":"Augustin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian M.","family":"Karsten","sequence":"additional","affiliation":[{"name":"Institute of Systemic Inflammation Research University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Riemekasten","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University of L\u00fcbeck  L\u00fcbeck 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