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
Creators
- van Wesemael, Tineke J.1
- Ajeganova, Sofia1
- Humphreys, Jennifer2
- Terao, Chikashi3
- Muhammad, Ammar1
- Symmons, Deborah P. M.2
- MacGregor, Alex J.4
- Hafström, Ingiäld5
- Trouw, Leendert A.1
- van der Helm-van Mil, Annette H. M.1
- Huizinga, Tom W. J.1
- Mimori, Tsuneyo6
- Toes, René E. M.1
- Matsuda, Fumihiko3
- Svensson, Björn7
- Verstappen, Suzanne M. M.2
- van der Woude, Diane1
- 1. Department of Rheumatology C1-R, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands
- 2. Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK
- 3. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- 4. Norwich Medical School, University of East Anglia, Norwich, UK
- 5. Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
- 6. Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- 7. Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden
Description
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.
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13075_2016_Article_1177.pdf
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