Background/Purpose:

Smoking is a risk factor for several autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Smoking is also a major risk factor for cardiovascular disease (CVD), both in the general population and in SLE. Smoking has furthermore been specifically associated with the occurrence of autoantibodies in RA, SLE and also in animal studies of autoimmune diseases.

We investigated the associations between patients smoking history and a set of autoantibodies in SLE. We also studied the potential interaction between smoking and autoantibodies for the occurrence of previous vascular events.   

Methods:

367 prevalent SLE patients from a single center were included. Clinical evaluation, history of previous vascular events and data on smoking habits and estimated number of smoked cigarettes were recorded at inclusion. Autoantibodies: anti(a)dsDNA, aSm, aRo52, a Ro60, aSSB and antiphospholipid (aPL) antibodies (anticardiolipin antibodies (aCL) IgG/IgM/IgA, anti-b₂ glycoprotein-1 (ab₂GP1) IgG/IgM/IgA) and the lupus anticoagulant (LAC) were measured using ELISA and multiplex methods. Association analyses between smoking status (ever, former, current) at inclusion and antibody status were performed through logistic regression. These variables were also investigated in relation to history of CVD through interaction analysis. Never smokers were used as reference.

Results:

In a first screening we noted that ever smoking was positively associated with aCL IgG (p=0.007), ab₂GP1 (p=0.002) and a positive LAC test (p=0.001) while the other investigated antibodies were not associated. Further analyses of the observed associations between aPL and smoking in multivariable models (including age, sex, age at disease onset, current smoking and former smoking) demonstrated that specifically former smoking was associated with LAC positivity OR 3.1(95% CI 1.6-5.9), ab₂GP1 IgG OR 3.1(95% CI 1.6-6.1) and aCL IgG OR 2.9(95% CI 1.6-5.8). The amount of cigarettes smoked did not affect aPL status. Interaction analysis demonstrated an interaction between occurrence of any aPL and ever smoking for the risk of venous thromboembolism (VTE), OR 2.8 (95% CI 1.3 – 5.9), attributable proportion due to interaction (AP)=0.66, p<0.05.

Conclusion:

We demonstrate that among SLE patients ever smoking, and in particular former smoking, is associated with pro-thrombotic aPL. Furthermore, the combination of smoking and aPL positivity seems to interact and enhance the risk of vascular events. Our results demonstrate associations between smoking, an environmental exposure, humoral immunity and vascular events in SLE. Further studies are needed to investigate the directions and mechanisms behind these associations. Our results further underscore the importance of advocating a smoke free lifestyle among SLE patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/smoking-autoantibodies-and-vascular-events-in-systemic-lupus-erythematosus/