{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:18:44Z","timestamp":1793686724965,"version":"4.5.1"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,5,23]],"date-time":"2010-05-23T00:00:00Z","timestamp":1274572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether antibodies against peptidyl arginine deiminase type 4 (PAD\u20104) are present in the preclinical phase of rheumatoid arthritis (RA) and to compare the timing and extent of their appearance with those of other preclinical autoantibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Prediagnosis serum samples from 83 patients with RA were evaluated for the presence of anti\u2013PAD\u20104 antibody, anti\u2013cyclic citrullinated peptide (anti\u2010CCP) antibody, and rheumatoid factor. In addition, a control cohort (n = 83) matched by age, sex, race, number of serum samples, and duration of serum storage was tested for the presence of anti\u2013PAD\u20104 antibody to determine its sensitivity and specificity for the subsequent development of RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen of 83 patients with RA (18.1%) had at least 1 prediagnosis sample positive for anti\u2013PAD\u20104. One of 83 control subjects (1.2%) had at least 1 positive sample, resulting in a sensitivity and specificity of 18.1% and 98.8%, respectively, of anti\u2013PAD\u20104 for the future development of RA. The mean duration of anti\u2013PAD\u20104 positivity prior to clinical diagnosis was 4.67 years. Anti\u2013PAD\u20104 positivity was associated with anti\u2010CCP positivity (odds ratio 5.13 [95% confidence interval 1.07\u201324.5]). In subjects with prediagnosis samples that were positive for both antibodies, anti\u2010CCP positivity predated anti\u2013PAD\u20104 positivity in 9 of 13 cases (69%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Autoantibodies to PAD\u20104 are present during the preclinical phase of RA in a subset of patients and are associated with anti\u2010CCP positivity. Further exploration is needed regarding the timing of appearance and disease\u2010related effects of PAD\u20104 autoimmunity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27570","type":"journal-article","created":{"date-parts":[[2010,5,26]],"date-time":"2010-05-26T15:20:52Z","timestamp":1274887252000},"page":"2633-2639","source":"Crossref","is-referenced-by-count":131,"title":["Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis"],"prefix":"10.1002","volume":"62","author":[{"given":"Jason R.","family":"Kolfenbach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lezlie A.","family":"Derber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin I.","family":"O'Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Gilliland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jess D.","family":"Edison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Darrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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