{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:23:04Z","timestamp":1791141784574,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2005,9,30]],"date-time":"2005-09-30T00:00:00Z","timestamp":1128038400000},"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":[[2005,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Recent data have shown that the most prominent and longest known genetic risk factors for rheumatoid arthritis (RA), HLA\u2013DRB1 shared epitope alleles, are only associated with RA that is characterized by the presence of antibodies against cyclic citrullinated peptide (anti\u2010CCP antibodies) and not with anti\u2010CCP\u2013negative RA. We undertook this study to investigate whether anti\u2010CCP\u2013negative RA is associated with other HLA\u2013DRB1 alleles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HLA typing was performed for 377 patients from the Leiden Early Arthritis Clinic who were diagnosed as having RA within the first year of followup (206 anti\u2010CCP\u2013positive patients and 171 anti\u2010CCP\u2013negative patients), 235 patients who, after 1 year, had undifferentiated arthritis (UA) (28 anti\u2010CCP\u2013positive patients and 207 anti\u2010CCP\u2013negative patients), and 423 healthy control subjects. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for HLA\u2013DRB1 allele frequencies were determined for all patient groups compared with the healthy control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HLA\u2013DR3 was more frequently present in the anti\u2010CCP\u2013negative RA group than in the control group (OR 1.84, 95% CI 1.26\u20132.67). This was not the case for anti\u2010CCP\u2013positive RA (OR 0.92, 95% CI 0.60\u20131.40). HLA\u2013DR3 was also more frequently present in anti\u2010CCP\u2013negative UA patients (OR 1.59, 95% CI 1.10\u20132.28), but not in anti\u2010CCP\u2013positive UA patients (OR 0.68, 95% CI 0.17\u20131.92).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HLA\u2013DR3 is associated with anti\u2010CCP\u2013negative arthritis and not with anti\u2010CCP\u2013positive arthritis. These data show that distinct genetic risk factors are associated with the presence of anti\u2010CCP antibodies in RA and indicate that different pathogenetic mechanisms underlie anti\u2010CCP\u2013positive and anti\u2010CCP\u2013negative RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21302","type":"journal-article","created":{"date-parts":[[2005,9,30]],"date-time":"2005-09-30T18:50:38Z","timestamp":1128106238000},"page":"3058-3062","source":"Crossref","is-referenced-by-count":154,"title":["Association of HLA\u2013DR3 with anti\u2013cyclic citrullinated peptide antibody\u2013negative rheumatoid arthritis"],"prefix":"10.1002","volume":"52","author":[{"given":"Kirsten N.","family":"Verpoort","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris A.","family":"van Gaalen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette H. M.","family":"van der Helm\u2010van Mil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geziena M. T.","family":"Schreuder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand C.","family":"Breedveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W. J.","family":"Huizinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene R. P.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene E. 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