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In the present study, we analysed the immunoglobulin (Ig)G subclasses regarding reactivity against cyclic citrullinated peptides (anti-CCP) among 504 clinically well-characterized patients with recent-onset RA in relation to smoking habits, shared epitope (SE) status and IgA and pan-IgG anti-CCP antibodies. All patients, regardless of pan-IgG anti-CCP status, were analysed for IgG1\u20134 CCP reactivity. Sixty-nine per cent were positive in any IgG anti-CCP subclass, and of these 67% tested positive regarding IgG1, 35% IgG2, 32% IgG3, and 59% IgG4 anti-CCP. Among ever-smokers the percentages of IgG2 anti-CCP (P\u2009=\u20090\u00b701) and IgA anti-CCP (P\u2009=\u20090\u00b7002)-positive cases were significantly higher compared to never-smokers. A positive IgG anti-CCP subclass -negative cases. Combining SE and smoking data revealed that IgG1 and IgG4 anti-CCP were the IgG anti-CCP isotypes associated with expression of SE, although the lower number of patients positive for IgG2 or IgG3 anti-CCP could, however, have influenced the results. High levels of IgG2 anti-CCP were shown to correlate with expression of the \u2018non-SE\u2019 allele human leucocyte antigen (HLA)-DRB1*15. In conclusion, in this study we describe different risk factor characteristics across the IgG anti-CCP subclasses, where IgG2 appears similar to IgA anti-CCP regarding the predominant association with smoking, while IgG1 and IgG4 related more distinctly to the carriage of SE genes.<\/jats:p>","DOI":"10.1111\/cei.12901","type":"journal-article","created":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T23:23:30Z","timestamp":1479425010000},"page":"53-62","source":"Crossref","is-referenced-by-count":10,"title":["Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)"],"prefix":"10.1093","volume":"188","author":[{"given":"K","family":"Martinsson","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Kastbom","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Skogh","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Link\u00f6ping University, Link\u00f6ping, 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