{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:40:56Z","timestamp":1778852456702,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PR120641"],"award-info":[{"award-number":["PR120641"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"Objective<\/jats:title>To explore the intrinsic role of inhibitor of DNA<\/jats:styled-content> binding 1 (ID<\/jats:styled-content>\u20101) in rheumatoid arthritis (RA<\/jats:styled-content>) fibroblast\u2010like synoviocytes (FLS<\/jats:styled-content>) and to investigate whether ID<\/jats:styled-content>\u20101 is citrullinated and autoantigenic in RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>RA<\/jats:styled-content> patient serum ID<\/jats:styled-content>\u20101 levels were measured before and after infliximab treatment. RA FLS<\/jats:styled-content> were transfected with a clustered regularly interspaced short palindromic repeat (CRISPR<\/jats:styled-content>)\/CRISPR<\/jats:styled-content>\u2010associated protein 9 construct targeting ID<\/jats:styled-content>\u20101 to examine the effects of ID<\/jats:styled-content>\u20101 deletion. RA<\/jats:styled-content> synovial fluid (SF<\/jats:styled-content>) and homogenized synovial tissue (ST<\/jats:styled-content>) were immunoprecipitated for ID<\/jats:styled-content>\u20101 and measured for citrullinated residues using an enzyme\u2010linked immunosorbent assay and Western blotting. Liquid chromatography tandem mass spectrometry (LC<\/jats:styled-content>\u2010MS<\/jats:styled-content>\/MS<\/jats:styled-content>) was performed on in vitro\u2013citrullinated recombinant human ID<\/jats:styled-content>\u20101 (cit\u2013ID<\/jats:styled-content>\u20101) to localize the sites of citrullination. Normal and RA<\/jats:styled-content> sera and SF<\/jats:styled-content> were analyzed by immunodot blotting for anti\u2013citrullinated protein antibodies (ACPA<\/jats:styled-content>s) to cit\u2013ID<\/jats:styled-content>\u20101.<\/jats:p><\/jats:sec>Results<\/jats:title>RA<\/jats:styled-content> patient serum ID<\/jats:styled-content>\u20101 levels positively correlated with several disease parameters and were reduced after infliximab treatment. RA FLS<\/jats:styled-content> displayed reduced growth and a robust increase in interleukin\u20106 (IL<\/jats:styled-content>\u20106) and IL<\/jats:styled-content>\u20108 production upon deletion of ID<\/jats:styled-content>\u20101. ID<\/jats:styled-content>\u20101 immunodepletion significantly reduced the levels of citrullinated residues in RA SF<\/jats:styled-content>, and citrullinated ID<\/jats:styled-content>\u20101 was detected in homogenized RA ST<\/jats:styled-content> (n = 5 samples; P<\/jats:italic> < 0.05). Immunodot blot analyses revealed ACPA<\/jats:styled-content>s to cit\u2013ID<\/jats:styled-content>\u20101 but not to native ID<\/jats:styled-content>\u20101, in RA<\/jats:styled-content> peripheral blood (PB<\/jats:styled-content>) sera (n = 30 samples; P<\/jats:italic> < 0.001) and SF<\/jats:styled-content> (n = 18 samples; P<\/jats:italic> < 0.05) but not in normal PB<\/jats:styled-content> sera. Following analyses of LC<\/jats:styled-content>\u2010MS<\/jats:styled-content>\/MS<\/jats:styled-content> results for citrullination sites and corresponding reactivity in immunodot assays, we determined the critical arginines in ID<\/jats:styled-content>\u20101 for autoantigenicity: R33, R52, and R121.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Novel roles of ID<\/jats:styled-content>\u20101 in RA<\/jats:styled-content> include regulation of FLS<\/jats:styled-content> proliferation and cytokine secretion as well as autoantigenicity following citrullination.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40886","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T16:10:37Z","timestamp":1552407037000},"page":"1241-1251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Citrullinated Inhibitor of DNA<\/scp> Binding 1 Is a Novel Autoantigen in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"71","author":[{"given":"Ray A.","family":"Ohara","sequence":"first","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautam","family":"Edhayan","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie M.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Isozaki","sequence":"additional","affiliation":[{"name":"Showa University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henriette A.","family":"Remmer","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Lanigan","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip L.","family":"Campbell","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G.","family":"Urquhart","sequence":"additional","affiliation":[{"name":"University of Michigan Health System and A. 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