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Smoking and HLA Genes in Rheumatoid Arthritis

An analysis from the Swedish EIRA incident rheumatoid arthritis cohort study shows that smoking and HLA-DRB1 exert differential effects on serologically defined rheumatoid arthritis (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 shared epitope has been confined to risk of seropositive RA. In this study, they further examined these risks based on RF and antiā€citrulline protein antibodies status.

This cohort study compared incident cases of RA (3,645) and matched controls (5,883) 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 shared epitope.

Key findings showed the highest risk in:

  • Double positive (RF+/anti-CCP2+) patients were most affected as smoking and HLA-DRB1 shared epitope conferred independent disease risks, and there was a strong interaction between the two risk factors
  • RF-/anti-CCP2+ subset: HLA-DRB1 shared epitope 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 shared epitope
  • 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.

Jack Cush, MD, is the director of clinical rheumatology at the Baylor Research Institute and a professor of medicine and rheumatology at Baylor University Medical Center in Dallas. He is the executive editor of A version of this article first appeared on RheumNow, a news, information, and commentary site dedicated to the field of rheumatology. Register to receive their free rheumatology newsletter.