Differing Effects of Smoking and HLA-DRB1 in Seropositive Rheumatoids Save

Analyses from the Swedish EIRA incident rheumatoid arthritis cohort study shows that smoking and HLA-DRB1 exert differential effects on serologically defined RA subsets - but that the strongest influence was seen in double positive (CCP+, RF+) individuals.

These investigators have previously shown that the strong interaction between smoking and HLA-DRB1 SE has been confined to risk of seropositive RA.  In this study they further examined these risks based on RF and ACPA status.

This cohort study compared incident cases of RA (3645) and matched controls (5883) based on the presence or absence of RF and anti-CCP2 antibodies. They assessed the risk for RA using subgroups based on seropositivity, smoking and the SE.

Key findings showed the highest risk in:

• Double positive (RF+/anti-CCP2+) patients were most affected as smoking and HLA-DRB1 SE conferred independent disease risks, and there was a strong interaction between the two risk factors.
• RF-/anti-CCP2+ subset: HLA-DRB1 SE conferred an increased risk of RA whereas the independent influence of smoking was less, but there was a significant interaction between HLA-DRB1 and smoking.
• In the RF+/anti-CCP2- subset, there was a smaller  increased risk in smokers, only marginally affected by HLA-DRB1 SE
• Double negative (RF-/anti-CCP2-) subset, neither smoking nor HLA-DRB1SE conferred increased risk of disease.

These findings indicate weighted effects of smoking and HLA-DRB1, especially on seropositive RA patients.