{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:24:30Z","timestamp":1794014670432,"version":"4.8.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T00:00:00Z","timestamp":1598659200000},"content-version":"am","delay-in-days":247,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AR07534"],"award-info":[{"award-number":["T32 AR07534"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","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 &amp; Rheumatology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti\u2013citrullinated protein antibodies (ACPAs) pre\u2013rheumatoid arthritis (RA) diagnosis and post\u2013RA diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the Department of Defense Serum Repository we identified 214 RA cases and 210 matched controls. Up to 3 pre\u2013RA diagnosis and 1 post\u2013RA diagnosis serum samples per subject were tested for RF and for IgA, IgG, and IgM ACPAs. The timing and trajectories of elevations of autoantibodies were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Autoantibody levels were elevated in cases versus controls a mean of 17.9 years before RA diagnosis for IgG ACPA, 14.2 years for IgA\u2010RF, 7.2 years for IgM\u2010RF, 6.2 years for IgA ACPA, and 5.0 years for both IgM ACPA and IgG\u2010RF (<jats:italic>P<\/jats:italic> &lt; 0.01 for all comparisons). There were similar relationships for positive or negative autoantibody status, with cases first showing positivity for IgG ACPA 1.9 years pre\u2010RA and for IgA\u2010RF 1.7 years pre\u2010RA, followed by the other isotypes. Only IgA ACPA positivity was significantly increased in post\u2013RA diagnosis samples (19% 0\u20132 years pre\u2010RA versus 39% &gt;2 years post\u2013RA diagnosis; <jats:italic>P<\/jats:italic> = 0.04). All autoantibody levels demonstrated an early initial elevation, a period of stability, then an increase immediately before RA diagnosis. A pre\u2010RA endotype of early elevation of autoantibodies was associated with increased use of biologic therapy, and a higher prevalence of sicca symptoms and lung disease post\u2013RA diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Differences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre\u2010RA endotypes may influence post\u2013RA diagnosis phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41091","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T03:04:23Z","timestamp":1567047863000},"page":"251-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"72","author":[{"given":"Lindsay B.","family":"Kelmenson","sequence":"first","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandie D.","family":"Wagner","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan K.","family":"McNair","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Frazer\u2010Abel","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Kristen","family":"Demoruelle","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan T.","family":"Bergstedt","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L.","family":"Feser","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura K.","family":"Moss","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Parish","sequence":"additional","affiliation":[{"name":"University of Colorado Denver Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Mewshaw","sequence":"additional","affiliation":[{"name":"Walter Reed National Military Medical Center  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-2272","authenticated-orcid":false,"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[{"name":"University of Nebraska  Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jess D.","family":"Edison","sequence":"additional","affiliation":[{"name":"Walter Reed National Military Medical Center  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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