{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:22:40Z","timestamp":1790468560779,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":88,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Centre for Clinical Research-Dalarna"},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Association Against Rheumatism"},{"name":"King Gustaf V's 80-Year Foundation"},{"name":"County Council of \u00d6sterg\u00f6tland"},{"name":"Reinhold Sund Foundation"},{"DOI":"10.13039\/501100007687","name":"Swedish Society of Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research County Council of South-East Sweden"},{"name":"Swedish Research Council for Health, Working Life, and Welfare"},{"DOI":"10.13039\/501100002706","name":"AFA Insurance","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002706","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Rheumatic Foundation"},{"name":"Innovative Medicines Initiative (BTCure)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Smoking and HLA\u2013DRB1\/shared epitope (SE) alleles are risk factors for rheumatoid arthritis (RA) characterized by seropositivity for antibodies targeting citrullinated proteins (ACPAs)\/cyclic citrullinated peptides (anti\u2010CCP). Previously, mainly IgG\u2010class antibodies have been studied. IgA\u2010class antibodies are to a great extent related to mucosal immunity. The aim of this study was to explore interrelations between cigarette smoking, presence of SE, and seropositivity for circulating IgA and\/or IgG anti\u2010CCP antibodies among patients with early RA, to determine whether ACPAs of the IgA subclass are regulated by different mechanisms than those of the IgG subclass.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two cohorts of patients with early RA, from the first Epidemiological Investigations of RA trial (n\u2009=\u20091,663) and the second Early Intervention in RA trial (n\u2009=\u2009199), were grouped into 4 subsets based on anti\u2010CCP subclass status (IgG\u2212\/IgA\u2212, IgG\u2212\/IgA+, IgG+\/IgA\u2212, and IgG+\/IgA+), and each subset was compared with regard to associations with smoking (current and former) and presence of SE. Interaction between smoking and SE was calculated using the attributable proportion (AP) due to interaction (assessing deviation from additivity of effects).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Smoking was overrepresented among IgA anti\u2010CCP\u2013positive RA patients, regardless of whether IgG anti\u2010CCP were present, whereas in patients with IgG anti\u2010CCP alone, no association with smoking was found. SE alleles were overrepresented among IgG anti\u2010CCP\u2013positive patients, regardless of IgA anti\u2010CCP status, and was not seen in patients with IgA anti\u2010CCP alone. An interaction between ever smoking and SE was found with regard to the risk of IgG+\/IgA+ RA (AP 0.5, 95% confidence interval 0.4, 0.6). No significant interaction was observed with regard to the risk of IgG\u2212\/IgA+ RA or IgG+\/IgA\u2212 RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with RA, a history of ever smoking was associated with seropositivity for IgA anti\u2010CCP antibodies, whereas presence of SE was associated with seropositivity for IgG anti\u2010CCP antibodies. An interaction between ever smoking and the SE was limited to the RA subset characterized by seropositivity for both IgG and IgA anti\u2010CCP. These findings provide novel evidence that anti\u2010CCP\u2013positive RA can be divided into at least 3 serologically distinct subsets associated with different risk factors, indicating different modes of pathogenesis in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39170","type":"journal-article","created":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T12:20:51Z","timestamp":1430137251000},"page":"2032-2037","source":"Crossref","is-referenced-by-count":51,"title":["Associations With Smoking and Shared Epitope Differ Between IgA\u2010 and IgG\u2010Class Antibodies to Cyclic Citrullinated Peptides in Early Rheumatoid Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Anna","family":"Sv\u00e4rd","sequence":"first","affiliation":[{"name":"Link\u00f6ping University, Link\u00f6ping, Sweden, and Falun Hospital Falun Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Skogh","sequence":"additional","affiliation":[{"name":"Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[{"name":"Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ilar","sequence":"additional","affiliation":[{"name":"Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Klareskog","sequence":"additional","affiliation":[{"name":"Karolinska Institutet and Karolinska University Hospital Solna Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alf","family":"Kastbom","sequence":"additional","affiliation":[{"name":"Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.053"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2012.723744"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4498"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.041079"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38201"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34344"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.075192"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090244"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22279"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2449"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.101086"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3237"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38066"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2012.04.011"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202747"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22845"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.016808"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","unstructured":"PadyukovL SilvaC StoltP AlfredssonL KlareskogL for theEpidemiological Investigation of Rheumatoid Arthritis Study Group.A gene\u2013environment interaction between smoking and shared epitope genes in HLA\u2013DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum2004;50:3085\u201392.","DOI":"10.1002\/art.20553"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.9.835"},{"key":"e_1_2_7_24_1","first-page":"51","volume-title":"Modern epidemiology","author":"Rothman KJ","year":"2008"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-011-9554-9"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.396"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.7.2676-2684.1997"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00234.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1992.tb07938.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.480"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1010-814"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201484"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.091355"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3383"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4039"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39170","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:41:14Z","timestamp":1759941674000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1002\/art.39170"],"URL":"https:\/\/doi.org\/10.1002\/art.39170","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]}}}