Hedstrom AK, et al. - Researchers compared 3,645 patients with rheumatoid arthritis (RA) and 5,883 matched controls to evaluate the interaction between smoking and HLA-DRB1 SE to determine risk in different RA subsets based on patients' rheumatoid factors (RF) and anti-citrulline protein antibodies (ACPA) status. They observed a strong interaction between both smoking and HLA-DRB1 SE in the RF+/anti-CCP2+ subset. HLA-DRB1 SE was associated with an increased risk of RA in the RF-/anti-CCP2+ subset, but smoking had limited independent influence. In the RF+/anti-CCP2- subset, they found an elevated risk in smokers; HLA-DRB1 SE had a marginal influence and no interaction was observed. Researchers did not find an increased risk of disease associated with smoking or HLA-DRB1SE in the RF-/anti-CCP2- patients.