{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:23:28Z","timestamp":1789604608548,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["866075"],"award-info":[{"award-number":["866075"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["PREVENT RA"],"award-info":[{"award-number":["PREVENT RA"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["nr. 772209"],"award-info":[{"award-number":["nr. 772209"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2021\u201002875"],"award-info":[{"award-number":["2021\u201002875"]}],"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":[[2023,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The appearance of anti\u2013citrullinated protein antibodies (ACPAs) in the circulation represents a major risk factor for developing rheumatoid arthritis (RA). Patient\u2010derived ACPAs have been shown to induce pain and bone erosion in mice, suggesting an active role in the pathogenicity of RA. We undertook this study to investigate whether ACPAs can induce tenosynovitis, an early sign of RA, in addition to pain and bone loss and whether these symptoms are dependent on peptidyl arginine deiminase 4 (PAD4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Monoclonal ACPAs generated from plasma cells of RA patients were transferred to wild\u2010type and PAD4\u2010deficient mice. Pain\u2010like behavior and macroscopic inflammation were monitored for a period of 4\u2009weeks, followed by the analyses of tenosynovitis in the ankle joints using magnetic resonance imaging (MRI) and bone microarchitecture in the tibia using an X\u2010ray microscope. Microscopic changes in the tendon sheath were analyzed in decalcified ankle joint sections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combination of 2 monoclonal ACPAs (1325:04C03 and 1325:01B09) induced long\u2010lasting pain\u2010like behavior and trabecular bone loss in mice. Although no synovitis was observed macroscopically, we detected tenosynovitis in the ACPA\u2010injected mice by MRI. Microscopic analyses of the joints revealed a cellular hyperplasia and a consequent enlargement of the tendon sheath in the ACPA\u2010treated group. In PAD4<jats:sup>\u2212\/\u2212<\/jats:sup> mice, the effects of ACPAs on pain\u2010like behavior, tenosynovitis, and bone loss were significantly reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Monoclonal ACPAs can induce tenosynovitis in addition to pain and bone loss via mechanisms dependent on PAD4\u2010mediated citrullination.<\/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\/art42320-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42320","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T15:33:57Z","timestamp":1659713637000},"page":"164-170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Combination of Two Monoclonal Anti\u2013Citrullinated Protein Antibodies Induced Tenosynovitis, Pain, and Bone Loss in Mice in a Peptidyl Arginine Deiminase\u20104\u2013Dependent Manner"],"prefix":"10.1002","volume":"75","author":[{"given":"Akilan","family":"Krishnamurthy","sequence":"first","affiliation":[{"name":"Department of Medicine, Rheumatology Unit Center of Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Circiumaru","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit Center of Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit Center of Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogan","family":"Kisten","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit Center of Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Damberg","sequence":"additional","affiliation":[{"name":"Karolinska Experimental Research and Imaging Centre (KERIC)  Stockholm 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivianne","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit Center of Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7980-4631","authenticated-orcid":false,"given":"Camilla I.","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Center for Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aase","family":"Hensvold","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit Center of Molecular Medicine, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca 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