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Rheumatoid Arthritis Clinical Studies
Association of smoking with the constitution of the anti–cyclic citrullinated peptide response in the absence of HLA–DRB1 shared epitope alleles†
Article first published online: 30 AUG 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 9, pages 2913–2918, September 2007
How to Cite
Verpoort, K. N., Papendrecht-van der Voort, E. A. M., van der Helm-van Mil, A. H. M., Jol-van der Zijde, C. M., van Tol, M. J. D., Drijfhout, J. W., Breedveld, F. C., de Vries, R. R. P., Huizinga, T. W. J. and Toes, R. E. M. (2007), Association of smoking with the constitution of the anti–cyclic citrullinated peptide response in the absence of HLA–DRB1 shared epitope alleles. Arthritis & Rheumatism, 56: 2913–2918. doi: 10.1002/art.22845
- Issue published online: 30 AUG 2007
- Article first published online: 30 AUG 2007
- Manuscript Accepted: 18 MAY 2007
- Manuscript Received: 9 NOV 2006
- European Communities Sixth Framework Programme. Grant Number: project 018661 Autocure
- Vidi grant from the Netherlands Organization for Scientific Research
Smoking is a risk factor for anti–cyclic citrullinated peptide (anti-CCP) antibody–positive rheumatoid arthritis (RA) in patients with HLA–DRB1 shared epitope (SE) alleles. It is unknown whether smoking influences not only the presence of these antibodies, but also other characteristics of the anti-CCP response, such as isotype usage. The aim of this study was to determine the influence of smoking on anti-CCP isotypes in RA patients, and to determine whether this influence is observed in the presence and/or absence of SE alleles.
IgA, IgM, and IgG subclasses of anti-CCP antibodies were measured by enzyme-linked immunosorbent assay in serum obtained at the first visit to the Leiden Early Arthritis Clinic from 216 patients with anti-CCP–positive RA whose smoking habits were also assessed. HLA genotyping data were available for 202 of these patients.
IgA and IgM anti-CCP 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-CCP, except IgG3, were significantly higher (P < 0.05) in smokers. The number of anti-CCP isotypes was higher in smokers compared with nonsmokers, both in SE-negative RA (P = 0.04) and in SE-positive RA (P = 0.07).
Patients with anti-CCP–positive RA who have a current or former tobacco exposure display a more extensive anti-CCP isotype usage in general, and IgA and IgM in particular, compared with patients with anti-CCP–positive RA who have never smoked. In contrast to its influence on the incidence of anti-CCP positivity, the influence of tobacco exposure on the constitution of the anti-CCP response is significant in SE-negative RA. These findings suggest a differential effect of tobacco exposure on the induction as compared with the propagation of the anti-CCP antibody response.