{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:07:58Z","timestamp":1791612478870,"version":"4.3.4"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2005,6,14]],"date-time":"2005-06-14T00:00:00Z","timestamp":1118707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,6,14]],"date-time":"2005-06-14T00:00:00Z","timestamp":1118707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course.<\/jats:p>","DOI":"10.1186\/ar1767","type":"journal-article","created":{"date-parts":[[2005,6,14]],"date-time":"2005-06-14T19:21:07Z","timestamp":1118776867000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":418,"title":["Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis"],"prefix":"10.1186","volume":"7","author":[{"given":"Annette HM","family":"van der Helm-van 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":"Ren\u00e9 EM","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom WJ","family":"Huizinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,6,14]]},"reference":[{"key":"1646_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar1027","volume":"6","author":"ER Vossenaar","year":"2004","unstructured":"Vossenaar ER, Zendman AJ, Van Venrooij WJ: Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis. Arthritis Res Ther. 2004, 6: 1-5. 10.1186\/ar1027.","journal-title":"Arthritis Res Ther"},{"key":"1646_CR2","doi-asserted-by":"publisher","first-page":"3485","DOI":"10.1002\/art.20584","volume":"50","author":"ER Vossenaar","year":"2004","unstructured":"Vossenaar ER, Smeets TJ, Kraan MC, Raats JM, van Venrooij WJ, Tak PP: The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum. 2004, 50: 3485-3494. 10.1002\/art.20584.","journal-title":"Arthritis Rheum"},{"key":"1646_CR3","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1002\/art.11223","volume":"48","author":"S Rantapaa-Dahlqvist","year":"2003","unstructured":"Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ: Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003, 48: 2741-2749. 10.1002\/art.11223.","journal-title":"Arthritis Rheum"},{"key":"1646_CR4","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1002\/art.20018","volume":"50","author":"MM Nielen","year":"2004","unstructured":"Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BAC: Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004, 50: 380-386. 10.1002\/art.20018.","journal-title":"Arthritis Rheum"},{"key":"1646_CR5","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1002\/art.20316","volume":"50","author":"FA Van Gaalen","year":"2004","unstructured":"Van Gaalen FA, van Aken J, Huizinga TW, Schreuder GM, Breedveld FC, Zanelli E, van Venrooij WJ, Verweij CL, Toes REM, de Vries RRP: Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis. Arthritis Rheum. 2004, 50: 2113-2121. 10.1002\/art.20316.","journal-title":"Arthritis Rheum"},{"key":"1646_CR6","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1136\/ard.2003.014233","volume":"63","author":"K Forslind","year":"2004","unstructured":"Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson B, BARFOT Study Group: Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004, 63: 1090-1095. 10.1136\/ard.2003.014233.","journal-title":"Ann Rheum Dis"},{"issue":"5 Suppl 31","key":"1646_CR7","first-page":"S100","volume":"21","author":"J Van Aken","year":"2003","unstructured":"Van Aken J, Bilsen JAM, Allaart CF, Huizinga TWJ, Breedveld FC: The Leiden Early Arthritis Clinic. Clin Exp Rheumatol. 2003, 21 (5 Suppl 31): S100-S105.","journal-title":"Clin Exp Rheumatol"},{"key":"1646_CR8","first-page":"10","volume-title":"EULAR Handbook of Clinical Assessments in Rheumatoid Arthritis","author":"PL Van Riel","year":"2000","unstructured":"Van Riel PL, van Gestel AM, Scott DG: EULAR Handbook of Clinical Assessments in Rheumatoid Arthritis. 2000, Alphen aan den Rijn: Van Zuiden Communications, 10-11."},{"key":"1646_CR9","first-page":"459","volume":"16","author":"B Hernandez-Cruz","year":"1998","unstructured":"Hernandez-Cruz B, Cardiel MH: Intra-observer reliability of commonly used outcome measures in rheumatoid arthritis. 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Clin Chim Acta. 2004, 350: 17-34. 10.1016\/j.cccn.2004.07.016.","journal-title":"Clin Chim Acta"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar1767.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar1767\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar1767.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T06:37:59Z","timestamp":1728369479000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar1767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,14]]},"references-count":15,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2005,9]]}},"alternative-id":["1646"],"URL":"https:\/\/doi.org\/10.1186\/ar1767","relation":{},"ISSN":["1478-6354"],"issn-type":[{"value":"1478-6354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,14]]},"assertion":[{"value":"23 March 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2005","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2005","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2005","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R949"}}