{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:09:42Z","timestamp":1770329382389,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","award":["R\u2010754141"],"award-info":[{"award-number":["R\u2010754141"]}],"id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007857","name":"Stiftelsen Konung Gustaf V:s 80-\u00e5rsfond","doi-asserted-by":"publisher","award":["FAI\u20102017\u20100420"],"award-info":[{"award-number":["FAI\u20102017\u20100420"]}],"id":[{"id":"10.13039\/501100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","award":["SLS\u2010682741"],"award-info":[{"award-number":["SLS\u2010682741"]}],"id":[{"id":"10.13039\/501100007687","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":[[2022,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate levels and possible extramucosal formation of secretory Ig, including anti\u2013citrullinated protein antibodies (ACPAs), in rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three patient groups were studied: 1) ACPA\u2010positive patients with musculoskeletal pain without clinical arthritis, 2) patients with recent\u2010onset RA, and 3) patients with established RA. In baseline serum samples (groups 1 and 2) and paired synovial fluid samples (group 3), we analyzed total secretory IgA, total secretory IgM, free secretory component (SC), and SC\u2010containing ACPA. Extramucosal formation of SC\u2010containing ACPA was investigated by preincubating RA sera and affinity\u2010purified ACPA with recombinant free SC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to healthy controls, serum levels of total secretory IgA and total secretory IgM were increased both in patients with early RA and at\u2010risk patients (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Patients with early RA with elevated total secretory Ig had significantly higher disease activity during the 3\u2010year follow\u2010up period compared to those without increased levels. At\u2010risk patients who developed arthritis during follow\u2010up (39 of 82) had higher baseline total secretory IgA levels compared to those who did not (<jats:italic>P<\/jats:italic>\u2009=\u20090.041). In established RA, total secretory IgA and total secretory IgM levels were higher in serum than in synovial fluid (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001), but SC\u2010containing ACPAs adjusted for total secretory Ig concentration were higher in synovial fluid (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). Preincubation with recombinant free SC yielded increased SC\u2010containing ACPA reactivity in sera as well as in affinity\u2010purified IgA and IgM ACPA preparations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Circulating secretory Ig are elevated before and at RA onset. In the presence of free SC, secretory Ig may form outside the mucosa, and SC\u2010containing ACPAs are enriched in RA joints. These findings shed important new light on the mucosal connection in RA development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42044","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T04:19:49Z","timestamp":1639973989000},"page":"801-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-9172","authenticated-orcid":false,"given":"Klara","family":"Martinsson","sequence":"first","affiliation":[{"name":"Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lovisa Lyttbacka","family":"Kling","sequence":"additional","affiliation":[{"name":"Link\u00f6ping University  Link\u00f6ping 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