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Multicenter Study
. 2016 Dec 1;18(1):285.
doi: 10.1186/s13075-016-1177-9.

Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se: a multicenter cohort study

Tineke J van Wesemael  1 , Sofia Ajeganova  2   3 , Jennifer Humphreys  4 , Chikashi Terao  5   6   7   8   9 , Ammar Muhammad  2 , Deborah P M Symmons  4   10 , Alex J MacGregor  11 , Ingiäld Hafström  3 , Leendert A Trouw  2 , Annette H M van der Helm-van Mil  2 , Tom W J Huizinga  2 , Tsuneyo Mimori  12 , René E M Toes  2 , Fumihiko Matsuda  5 , Björn Svensson  13 , Suzanne M M Verstappen  4 , Diane van der Woude  2
Affiliations
Multicenter Study

Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se: a multicenter cohort study

Tineke J van Wesemael et al. Arthritis Res Ther. .

Abstract

Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies.

Methods: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals without RA. Furthermore, RA patients fulfilling the 1987 criteria from three early arthritis cohorts from the Netherlands (n = 678), the United Kingdom (n = 761), and Sweden (n = 795) were used. Data on smoking, RF, anti-CCP2, and anti-CarP were available. A total score of autoantibodies was calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by logistic regression.

Results: In the population-based non-RA cohort, no association was found between smoking and one autoantibody (RF or anti-CCP2), but smoking was associated with double-autoantibody positivity (OR 2.95, 95% CI 1.32-6.58). In RA patients, there was no association between smoking and the presence of one autoantibody (OR 0.99, 95% CI 0.78-1.26), but smoking was associated with double-autoantibody positivity (OR 1.32, 95% CI 1.04-1.68) and triple-autoantibody positivity (OR 2.05, 95% CI 1.53-2.73).

Conclusions: Smoking is associated with the concurrent presence of multiple RA-associated autoantibodies rather than just ACPA. This indicates that smoking is a risk factor for breaking tolerance to multiple autoantigens in RA.

Keywords: Anti-carbamylated protein antibodies; Anti-citrullinated protein antibodies; Rheumatoid arthritis; Rheumatoid factor; Risk factor; Smoking.

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Figures

Fig. 1
Fig. 1
Pooled analysis investigating the association between smoking and the number of autoantibodies. Forest plots with odds ratio (OR) and 95% confidence interval. a Association of smoking with one autoantibody versus zero autoantibodies. b Association of smoking with two autoantibodies versus zero autoantibodies. c Association of smoking with three autoantibodies versus zero autoantibodies. d Association of smoking with three autoantibodies versus two autoantibodies. BARFOT Better Anti‐Rheumatic Farmaco-Therapy, EAC Early Arthritis Clinic, NOAR Norfolk Arthritis Register
See this image and copyright information in PMC

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