{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:35:49Z","timestamp":1790984149219,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008021","name":"Bristol Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30\u2010AR\u2010070254"],"award-info":[{"award-number":["P30\u2010AR\u2010070254"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["F31\u2010AR\u2010077406"],"award-info":[{"award-number":["F31\u2010AR\u2010077406"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","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":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Autoantibodies targeting peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination, are found in a subset of patients with rheumatoid arthritis (RA) with severe joint disease. However, the mechanisms by which anti\u2010PAD4 antibodies participate in disease pathogenesis are incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the role of anti\u2010PAD4 monoclonal antibodies derived from patients with RA using a collagen\u2010induced arthritis (CIA) mouse model and human monocyte in vitro cultures. The cellular targets of anti\u2010PAD4 antibodies were identified using mouse knee joint cells and human peripheral blood mononuclear cells. In addition, PAD4 gene and protein expression was assessed using human fibroblast\u2010like synoviocyte in vitro cultures and a single\u2010cell RNA sequencing data set obtained from patients with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that anti\u2010PAD4 antibody treatment augmented disease severity in the CIA mouse model, with increased joint damage, myeloid cell infiltration, and synovial fibroblast activation. Arthritic mice administered with anti\u2010PAD4 antibodies had an increased proportion of interleukin\u201017A (IL\u201017A), tumor necrosis factor \u03b1 (TNF\u03b1), and interferon\u2010\u03b3 (IFN\u03b3)\u2013producing T cells. Anti\u2010PAD4 antibodies preferentially bound monocytes in both humans and mice, eliciting proinflammatory chemokine production by human monocytes in vitro. T cell cytokines enhanced by anti\u2010PAD4 antibodies in the CIA model (ie, IL\u201017A, TNF\u03b1, and IFN\u03b3) synergized to induce a proinflammatory phenotype in human fibroblast\u2010like synoviocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest a model in which anti\u2010PAD4 antibody binding to monocytes triggers an inflammatory cascade that promotes immune cell recruitment to the joint and T cell activation, culminating in synovial fibroblast activation and the development of more severe arthritis.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art43168-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43168","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T01:00:10Z","timestamp":1743642010000},"page":"1150-1165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti\u2013Peptidylarginine Deiminase 4 Autoantibodies Derived From Patients With Rheumatoid Arthritis Exert Pathogenic Effects by Activating Monocytes and Exacerbating Inflammatory Arthritis"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-2016","authenticated-orcid":false,"given":"Taejoon","family":"Won","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland, and College of Veterinary Medicine 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