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).
abstract: Given the possible importance of anti-citrullinated peptide/protein antibodies (ACPA) for initiation and progression of rheumatoid arthritis (RA), extended knowledge about the different isotypes and subclasses is important. 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 IgG1-4 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 = 0·01) and IgA anti-CCP (P = 0·002)-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 'non-SE' 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Martinsson
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Kastbom
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Skogh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000209:etiology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology*; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012907:Smoking / Q000009:adverse effects*; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: IgG subclasses; cyclic citrullinated peptide; rheumatoid arthritis; shared epitope; smoking