{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:45:34Z","timestamp":1793313934092,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T00:00:00Z","timestamp":1374796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH (National Institute for Arthritis and Musculoskeletal and Skin Diseases)","award":["R01-AR-051394"],"award-info":[{"award-number":["R01-AR-051394"]}]},{"name":"NIH (National Institute for Arthritis and Musculoskeletal and Skin Diseases)","award":["T32-AR-007534-25"],"award-info":[{"award-number":["T32-AR-007534-25"]}]},{"name":"National Institute of Allergy and Infectious Diseases Autoimmunity Prevention Center","award":["U19-AI-050864"],"award-info":[{"award-number":["U19-AI-050864"]}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"crossref","award":["Within Our Reach grant II-T-11-14"],"award-info":[{"award-number":["Within Our Reach grant II-T-11-14"]}],"id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007155","name":"Walter S. and Lucienne Driskill Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007155","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine reactivity to anti\u2013citrullinated protein\/peptide antibodies (ACPAs) and determine associations between ACPAs and other rheumatoid arthritis (RA)\u2013related autoantibodies and clinically assessed swollen or tender joints in unaffected first\u2010degree relatives of RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples were obtained from first\u2010degree relatives without RA according to the 1987 American College of Rheumatology (ACR) and the 2010 ACR\/European League Against Rheumatism classification criteria. A bead\u2010based assay was used to measure 16 separate ACPAs in sera from 111 antibody\u2010positive first\u2010degree relatives who were positive on at least 1 visit for any of 5 RA\u2010related autoantibodies (rheumatoid factor [RF], anti\u2013cyclic citrullinated peptide 2 [anti\u2013CCP\u20102], and RF isotypes), and sera from 99 antibody\u2010negative first\u2010degree relatives who were never autoantibody positive. Cutoffs for positivity for each ACPA were determined using receiver operating characteristic curves derived from data on 200 RA patients and 98 blood donor controls, in which positivity for \u22659 ACPAs had 92% specificity and 62% sensitivity for RA. In first\u2010degree relatives, ACPA reactivity was assessed, and associations between ACPAs (number positive, and positivity for \u22659 ACPAs) and RA\u2010related characteristics were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010seven percent of anti\u2013CCP\u20102\u2013positive first\u2010degree relatives and 8% of anti\u2013CCP\u20102\u2013 negative first\u2010degree relatives were positive for \u22659 ACPAs. After adjusting for age, sex, ethnicity, and pack\u2010years of smoking, an increasing number of ACPAs was directly associated with the presence of \u22651 tender joint on examination (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.04\u20131.34), with the greatest risk of having \u22651 tender joint seen in first\u2010degree relatives positive for \u22659 ACPAs (OR 5.00, 95% CI 1.37\u201318.18).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RA\u2010free first\u2010degree relatives (even those negative for RF and anti\u2013CCP\u20102) demonstrate reactivity to multiple ACPAs, and the presence of an increasing number of ACPAs may be associated with signs of joint inflammation. Prospective evaluation of the relationship between these findings and the progression of classifiable RA is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38022","type":"journal-article","created":{"date-parts":[[2013,6,10]],"date-time":"2013-06-10T14:13:17Z","timestamp":1370873597000},"page":"1995-2004","source":"Crossref","is-referenced-by-count":46,"title":["Relatives Without Rheumatoid Arthritis Show Reactivity to Anti\u2013Citrullinated Protein\/Peptide Antibodies That Are Associated With Arthritis\u2010Related Traits: Studies of the Etiology of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Kendra A.","family":"Young","sequence":"first","affiliation":[{"name":"Colorado School of Public Health Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lezlie A.","family":"Derber","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Hughes\u2010Austin","sequence":"additional","affiliation":[{"name":"Colorado School of Public Health Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"VA Palo Alto Health Care System, Palo Alto, and Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Sokolove","sequence":"additional","affiliation":[{"name":"VA Palo Alto Health Care System, Palo Alto, and Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Weisman","sequence":"additional","affiliation":[{"name":"Cedars\u2010Sinai Medical Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane H.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[{"name":"Omaha VA Medical Center and University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"O'Dell","sequence":"additional","affiliation":[{"name":"Omaha VA Medical Center and University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Keating","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K.","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research Manhasset New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Robinson","sequence":"additional","affiliation":[{"name":"VA Palo Alto Health Care System, Palo Alto, and Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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