{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:35:55Z","timestamp":1791279355736,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,3,29]],"date-time":"2006-03-29T00:00:00Z","timestamp":1143590400000},"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":[[2006,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The shared epitope (SE)\u2013containing HLA\u2013DRB1 alleles represent the most significant genetic risk factor for rheumatoid arthritis (RA). Recent studies indicate that the SE alleles are associated with only RA that is characterized by the presence of anti\u2013cyclic citrullinated peptide (anti\u2010CCP) antibodies, and not with anti\u2010CCP\u2013negative disease. In this study we investigated whether the SE alleles contribute to the development of anti\u2010CCP\u2013positive RA, or whether they are associated solely with the presence of anti\u2010CCP antibodies. We therefore determined the influence of the SE alleles and anti\u2010CCP antibodies on the progression from recent\u2010onset undifferentiated arthritis (UA) to RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with recent\u2010onset UA at the 2\u2010week visit (n = 570) were selected from the Leiden Early Arthritis Cohort. SE alleles, rheumatoid factor (RF) status, and anti\u2010CCP antibody levels were determined. Progression to RA or other diagnoses was monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred seventy\u2010seven patients with UA developed RA during the 1\u2010year followup, whereas the disease in 393 patients remained unclassified or was given other diagnoses. The SE alleles correlated with the presence of anti\u2010CCP antibodies, but not with the presence of RF. Both in SE\u2010positive and in SE\u2010negative patients with UA, the presence of anti\u2010CCP antibodies was significantly associated with the development of RA. More intriguingly, however, no apparent contribution of the SE alleles to the progression to RA was found when analyses were stratified according to the presence of anti\u2010CCP antibodies. In patients with anti\u2010CCP\u2013positive disease, the presence of SE alleles was associated with significantly higher levels of anti\u2010CCP antibodies, suggesting that the SE alleles act as classic immune response genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The SE alleles do not independently contribute to the progression to RA from UA, but rather contribute to the development of anti\u2010CCP antibodies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21739","type":"journal-article","created":{"date-parts":[[2006,3,30]],"date-time":"2006-03-30T02:47:58Z","timestamp":1143686878000},"page":"1117-1121","source":"Crossref","is-referenced-by-count":280,"title":["The HLA\u2013DRB1 shared epitope alleles are primarily a risk factor for anti\u2013cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis"],"prefix":"10.1002","volume":"54","author":[{"given":"Annette H. M.","family":"van der Helm\u2010van Mil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten N.","family":"Verpoort","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":"Ren\u00e9 E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 R. P.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3,29]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"1032","article-title":"HLA\u2010DRB1*0401\/0404 genotype and rheumatoid arthritis: increased association in men, young age at onset, and disease severity","volume":"22","author":"MacGregor A","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21385"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20044"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"issue":"31","key":"e_1_2_5_8_2","first-page":"S100","article-title":"The Leiden Early Arthritis Clinic","volume":"21","author":"Aken J","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.175.4019.273"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.21739","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.21739","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T21:18:34Z","timestamp":1698787114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.21739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,29]]},"references-count":8,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1002\/art.21739"],"URL":"https:\/\/doi.org\/10.1002\/art.21739","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3,29]]}}}