Background/Purpose: Smoking is associated with the presence of several autoantibodies in various autoimmune diseases. In rheumatoid arthritis (RA), smoking has been described to be specifically associated with the presence of anti-citrullinated protein antibodies (ACPA). We investigated whether smoking is specifically associated with ACPA-positive RA, or with autoantibody-positive RA in general.

Methods: A meta-analysis was performed using RA patients from 5 countries: Norway, Sweden, the United Kingdom, the Netherlands and Japan. Complete data on rheumatoid factor (RF)-, ACPA-status and tobacco exposure were available for 6320 RA patients. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the presence of RF, ACPA or both were calculated by logistic regression comparing ever smokers with never smokers, and using the RF-negative ACPA-negative RA patients as the reference category.

Results: There was no significant association between tobacco exposure and seropositive RA in patients who were positive for only one antibody, being either RF (OR 1.04, 0.76 – 1.42) or ACPA (OR 1.00, 0.82 – 1.22). However, smoking was significantly associated with double-positive (RF-positive and ACPA-positive) RA (OR 1.55, 1.20 – 2.00). When double-positive patients were compared to single-positive patients, the effect of the additional presence of RF or ACPA was comparable; OR for RF: 1.42 (1.20 – 1.67), OR for ACPA: 1.50 (1.26 – 1.79).

Conclusion: Smoking is not associated with ACPA-positive RA, but rather with the concurrent presence of RF and ACPA in RA patients. These data indicate that smoking predisposes to the development of multiple autoantibodies, and not exclusively to ACPA-positive RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-rheumatoid-arthritis-smoking-is-not-primarily-associated-with-anti-citrullinated-protein-antibodies-but-with-the-presence-of-multiple-autoantibodies/