{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:59:56Z","timestamp":1790805596010,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005689","name":"Gothenburg Medical Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005689","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010223","name":"Stiftelsen Jubileumsklinikens Forskningsfond mot Cancer","doi-asserted-by":"publisher","award":["190341Pj01H"],"award-info":[{"award-number":["190341Pj01H"]}],"id":[{"id":"10.13039\/501100010223","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017\u201006014"],"award-info":[{"award-number":["2017\u201006014"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"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 investigate potential associations between B cell\u2013related immunologic changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients who developed ICI\u2010induced IA (ICI\u2010IA) and patients who did not develop immune\u2010related adverse events (non\u2010IRAE) after receiving ICIs to treat metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI\u2010IA occurrence and at different time points during treatment. Peripheral blood B cell subsets during ICI treatment were analyzed by flow cytometry. Rheumatoid factor, anti\u2013citrullinated protein antibodies, and antibodies against joint\u2010related proteins were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Proportions of CD19+ B cells were higher in patients with ICI\u2010IA (n\u00a0=\u00a07) compared to patients with non\u2010IRAE (n\u00a0=\u00a015) (median 11.7% [interquartile range (IQR) 9.7\u201316.2%] versus 8.1% [IQR 5.7\u201311.0%]; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). The proportion and absolute numbers of transitional CD19+CD10+CD24<jats:sup>high<\/jats:sup>CD38<jats:sup>high<\/jats:sup> B cells were increased in patients with ICI\u2010IA compared to non\u2010IRAE patients (median 8.1% [IQR 4.9\u201312.1%] versus 3.6% [IQR 1.9\u20134.9%]; median 10.7 cells\/\u03bcl [IQR 8.9\u201319.6] versus 4.4 cells\/\u03bcl [IQR 2.3\u20136.6]; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01 for both). In addition, higher levels of transitional B cells were associated with development of ICI\u2010IA (odds ratio 2.25 [95% confidence interval 1.03\u20134.9], <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04). Transitional B cells increased before the onset of overt ICI\u2010IA and decreased between the active and quiescent stages of ICI\u2010IA (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). Autoantibodies to type II collagen epitopes were detected in up to 43% of ICI\u2010IA patients compared to none of the non\u2010IRAE patients (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Development of ICI\u2010IA is accompanied by an increase in transitional B cells and by production of autoantibodies to joint\u2010related proteins. Monitoring of B cell\u2013driven abnormalities upon ICI treatment may help earlier recognition of ICI\u2010IA.<\/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\/art42406-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42406","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T12:20:11Z","timestamp":1669033211000},"page":"856-863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Early Increase of Circulating Transitional B Cells and Autoantibodies to <scp>Joint\u2010Related<\/scp> Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor\u2013Induced Inflammatory Arthritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-1248","authenticated-orcid":false,"given":"Mariele","family":"Gatto","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, and Department of Medicine, Unit of Rheumatology University of Padova  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bjursten","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sahlgrenska University Hospital, and Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-7549","authenticated-orcid":false,"given":"Monica Leu","family":"Agelii","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Jonell","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"McGrath","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"L\u00f6nnblom","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Section for Medical Inflammation Research Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-8216","authenticated-orcid":false,"given":"Outi","family":"Sareila","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Section for Medical Inflammation Research Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-2576","authenticated-orcid":false,"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Section for Medical Inflammation Research Karolinska Institute  Stockholm 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-4844","authenticated-orcid":false,"given":"Inger","family":"Gjertsson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910836"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14316"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00364"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160801"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0160-6"},{"issue":"7","key":"e_1_2_7_7_1","article-title":"Mechanisms of immune\u2010related 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