van Wesemael Tineke J, Ajeganova Sofia, Humphreys Jennifer, Terao Chikashi, Muhammad Ammar, Symmons Deborah P M, MacGregor Alex J, Hafström Ingiäld, Trouw Leendert A, van der Helm-van Mil Annette H M, Huizinga Tom W J, Mimori Tsuneyo, Toes René E M, Matsuda Fumihiko, Svensson Björn, Verstappen Suzanne M M, van der Woude Diane
Department of Rheumatology C1-R, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Arthritis Res Ther. 2016 Dec 1;18(1):285. doi: 10.1186/s13075-016-1177-9.
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.
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.
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).
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.
吸烟对类风湿关节炎（RA）的影响据推测是通过抗瓜氨酸化蛋白抗体（ACPA）的形成介导的。然而，在RA中，自身抗体如ACPA、类风湿因子（RF）和抗氨甲酰化蛋白抗体（抗CarP）常常同时出现，因此尚不清楚吸烟是否与某些自身抗体而非其他抗体存在特异性关联。我们因此研究了吸烟是否仅与ACPA相关，还是与多种RA相关自身抗体的存在有关。
以日本人群为基础的队列（n = 9575）用于研究无RA个体中吸烟与RF及抗环瓜氨酸肽抗体（抗CCP2）之间的关联。此外，还纳入了来自荷兰（n = 678）、英国（n = 761）和瑞典（n = 795）的三个早期关节炎队列中符合1987年标准的RA患者。获取了吸烟、RF、抗CCP2和抗CarP的数据。计算自身抗体的总分，并通过逻辑回归计算比值比（OR）和95%置信区间（95%CI）。
在以人群为基础的非RA队列中，未发现吸烟与单一自身抗体（RF或抗CCP2）之间存在关联，但吸烟与双重自身抗体阳性相关（OR 2.95，95%CI 1.32 - 6.58）。在RA患者中，吸烟与单一自身抗体的存在之间无关联（OR 0.99，95%CI 0.78 - 1.26），但吸烟与双重自身抗体阳性相关（OR 1.32，95%CI 1.04 - 1.68）以及三重自身抗体阳性相关（OR 2.05，95%CI 1.53 - 2.73）。
吸烟与多种RA相关自身抗体的同时存在有关，而非仅与ACPA有关。这表明吸烟是RA中打破对多种自身抗原耐受性的一个危险因素。
