{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:42:00Z","timestamp":1791096120822,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2004,7,6]],"date-time":"2004-07-06T00:00:00Z","timestamp":1089072000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The functional role of HLA class II molecules in the pathogenesis of rheumatoid arthritis (RA) is unclear. HLA class II molecules are involved in the interaction between T and B lymphocytes required for long\u2010lived B cell responses and generation of high\u2010affinity IgG antibodies. We undertook this study to investigate the relationship between HLA class II gene polymorphisms and RA\u2010specific IgG antibodies against cyclic citrullinated peptides (anti\u2010CCP antibodies).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010resolution HLA\u2013DR and DQ typing and anti\u2013CCP\u20102 antibody testing were performed on 268 RA patients from the Early Arthritis Clinic cohort at the Department of Rheumatology of the Leiden University Medical Center. The presence of anti\u2010CCP antibodies was analyzed in carriers of the different DR and DQ alleles. Disease progression was measured over a period of 4 years by scoring radiographs of the hands and feet using the Sharp\/van der Heijde method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Carriership of the individual alleles HLA\u2013DRB1*0401, DRB1*1001, DQB1*0302, and DQB1*0501 was associated with the presence of anti\u2010CCP antibodies. Carriers of DQ\u2013DR genotypes containing proposed RA susceptibility alleles were significantly more often anti\u2010CCP antibody positive. Carriership of one or two HLA\u2013DRB1 shared epitope (SE) alleles was significantly associated with production of anti\u2010CCP antibodies (odds ratio [OR] 3.3, 95% confidence interval [95% CI] 1.8\u20136.0 and OR 13.3, 95% CI 4.6\u201340.4, respectively). An increased rate of joint destruction was observed in SE+, anti\u2010CCP+ patients (mean Sharp score 7.6 points per year) compared with that in SE\u2212, anti\u2010CCP+ patients (2.4 points per year) (<jats:italic>P<\/jats:italic> = 0.04), SE+, anti\u2010CCP\u2212 patients (1.6 points per year) (<jats:italic>P<\/jats:italic> &lt; 0.001), and SE\u2212, anti\u2010CCP\u2212 patients (1.6 points per year) (<jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HLA class II RA susceptibility alleles are associated with production of anti\u2010CCP antibodies. Moreover, more severe disease progression is found in RA patients with both anti\u2010CCP antibodies and SE alleles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20316","type":"journal-article","created":{"date-parts":[[2004,7,6]],"date-time":"2004-07-06T15:02:58Z","timestamp":1089126178000},"page":"2113-2121","source":"Crossref","is-referenced-by-count":308,"title":["Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis"],"prefix":"10.1002","volume":"50","author":[{"given":"Floris A.","family":"Van Gaalen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Van Aken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W. J.","family":"Huizinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geziena M. Th.","family":"Schreuder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand C.","family":"Breedveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Zanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walther J.","family":"Van Venrooij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis L.","family":"Verweij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 R. 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