Associations to smoking and shared epitope differ between IgA and IgG class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis
2015 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 67, no 8, 2032-2037 p.Article in journal (Refereed) Published
Background Smoking and HLA-DRB1/shared epitope (SE) are well-known interacting risk factors for developing rheumatoid arthritis (RA) with IgG anticitrullinated protein/peptide antibodies (ACPA). It remains unknown to what extent SE-genes and smoking associate with mucosal immune responses.
Objectives This study was done to explore relations between cigarette smoking habits and SE versus circulating IgA and IgG anti-cyclic citrullinated peptide antibodies (anti-CCP) among early RA patients.
Methods Patients from two early-RA cohorts were analysed, EIRA-1 (n=1663) and TIRA-2 (n=199). The patients were grouped into four subsets based on anti-CCP: IgG-/IgA-, IgG-/IgA+, IgG+/IgA- and IgG+/IgA+. Interaction between smoking and SE was calculated by the attributable proportion due to deviation from additivity. Analyzed controls (n=1100) were randomly selected from the EIRA-1 study base.
Results Anti-CCP occurrence was similar in the two cohorts. Only in EIRA was IgA anti-CCP detected alone in a minority of cases (3%). Smoking was significantly overrepresented among IgA anti-CCP+ patients with or without IgG-class anti-CCP, but not with IgG anti-CCP alone. Presence of SE genes was overrepresented among IgG anti-CCP+ patients with or without IgA-class anti-CCP, but not with IgA anti-CCP alone. Smoking and SE interacted regarding the risk of IgG+/IgA+ RA (AP=0.5, 95 % CI=0.4-0.6), whereas no significant interaction was observed regarding IgG-/IgA+ or IgG+/IgA- RA.
Conclusions Association between cigarette smoking and anti-CCP is limited to cases with IgA-class antibodies in addition to IgG anti-CCP. This suggests a causal relation between chronic mucosal irritation/inflammation, induction of a systemic IgA anti-CCP response and subsequent development of RA.
Place, publisher, year, edition, pages
2015. Vol. 67, no 8, 2032-2037 p.
Rheumatoid arthritis, immunoglobulin A, ACPA, smoking, shared epitope
Rheumatology and Autoimmunity
IdentifiersURN: urn:nbn:se:liu:diva-105986DOI: 10.1002/art.39170ISI: 000358609300007OAI: oai:DiVA.org:liu-105986DiVA: diva2:712605
At the defence date the status of this publication was Manuscript.
Supported by the Centre for Clinical Research-Dalarna, the Swedish Research Council, the Swedish Association Against Rheumatism, King Gustaf V's 80-Year Foundation, the County Council of Ostergotland, the Reinhold Sund Foundation, the Swedish Society of Medicine, the Medical Research County Council of South-East Sweden, the Swedish Research Council for Health, Working Life, and Welfare, AFA Insurance, the Swedish Rheumatic Foundation, and the Innovative Medicines Initiative (BTCure).2014-04-152014-04-152016-03-23Bibliographically approved