{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:35:24Z","timestamp":1791279324536,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T00:00:00Z","timestamp":1188432000000},"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":[[2007,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Smoking is a risk factor for anti\u2013cyclic citrullinated peptide (anti\u2010CCP) antibody\u2013positive rheumatoid arthritis (RA) in patients with HLA\u2013DRB1 shared epitope (SE) alleles. It is unknown whether smoking influences not only the presence of these antibodies, but also other characteristics of the anti\u2010CCP response, such as isotype usage. The aim of this study was to determine the influence of smoking on anti\u2010CCP isotypes in RA patients, and to determine whether this influence is observed in the presence and\/or absence of SE alleles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IgA, IgM, and IgG subclasses of anti\u2010CCP antibodies were measured by enzyme\u2010linked immunosorbent assay in serum obtained at the first visit to the Leiden Early Arthritis Clinic from 216 patients with anti\u2010CCP\u2013positive RA whose smoking habits were also assessed. HLA genotyping data were available for 202 of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IgA and IgM anti\u2010CCP were more frequent in RA patients who were smokers than in those who were nonsmokers (odds ratio 2.8 and 1.8, respectively). In addition, levels of all isotypes of anti\u2010CCP, except IgG3, were significantly higher (<jats:italic>P<\/jats:italic> &lt; 0.05) in smokers. The number of anti\u2010CCP isotypes was higher in smokers compared with nonsmokers, both in SE\u2010negative RA (<jats:italic>P<\/jats:italic> = 0.04) and in SE\u2010positive RA (<jats:italic>P<\/jats:italic> = 0.07).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with anti\u2010CCP\u2013positive RA who have a current or former tobacco exposure display a more extensive anti\u2010CCP isotype usage in general, and IgA and IgM in particular, compared with patients with anti\u2010CCP\u2013positive RA who have never smoked. In contrast to its influence on the incidence of anti\u2010CCP positivity, the influence of tobacco exposure on the constitution of the anti\u2010CCP response is significant in SE\u2010negative RA. These findings suggest a differential effect of tobacco exposure on the induction as compared with the propagation of the anti\u2010CCP antibody response.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22845","type":"journal-article","created":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T19:18:47Z","timestamp":1188501527000},"page":"2913-2918","source":"Crossref","is-referenced-by-count":41,"title":["Association of smoking with the constitution of the anti\u2013cyclic citrullinated peptide response in the absence of HLA\u2013DRB1 shared epitope alleles"],"prefix":"10.1002","volume":"56","author":[{"given":"K. N.","family":"Verpoort","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A. M.","family":"Papendrecht\u2010van der Voort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H. M.","family":"van der Helm\u2010van Mil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Jol\u2010van der Zijde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J. D.","family":"van Tol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. W.","family":"Drijfhout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. C.","family":"Breedveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. R. P.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. W. J.","family":"Huizinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,8,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20044"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.2.120"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25422"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21739"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(87)90082-5"},{"key":"e_1_2_6_7_2","first-page":"630","article-title":"The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis","volume":"27","author":"Wolfe F","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_6_8_2","first-page":"861","article-title":"Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients?","volume":"23","author":"Papadopoulos NG","year":"2005","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.041079"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22373"},{"issue":"5","key":"e_1_2_6_12_2","first-page":"S100","article-title":"The Leiden Early Arthritis Clinic","volume":"21","author":"Van Aken J","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22279"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(93)90143-O"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.48.11.1130"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.22845","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.22845","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T09:45:18Z","timestamp":1697017518000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.22845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,30]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2007,9]]}},"alternative-id":["10.1002\/art.22845"],"URL":"https:\/\/doi.org\/10.1002\/art.22845","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,30]]}}}