Background/Purpose:   Rheumatoid arthritis (RA) is characterized by the presence of circulating autoantibodies, which can be predictive of future RA development in currently unaffected individuals.  The specific etiology of RA is unknown; however, studies have suggested that respiratory exposures such as smoking and proximity to road traffic may be associated with development of RA.  To elucidate the relationship between respiratory exposures and explore the potential that inhaled exposures may act early in the pathogenesis of RA, leading to early generation of RA-related autoimmunity, we evaluated the association between exposure to air pollution, measured by yearly average particulate matter (PM) 2.5 and 10, and presence of RA-related autoantibodies.

Methods:   The Studies of the Etiology of Rheumatoid Arthritis (SERA) is a multicenter study evaluating first-degree relatives (FDRs) of a proband with RA.  FDRs lack classifiable RA at enrollment and are serially assessed for the presence of RA-related autoimmunity and potential risk factors for RA development.  Outcomes assessed were presence of rheumatoid factor (RF), and the High Risk profile (positive for anti-CCP autoantibody and/or ≥2 RF isotypes), demonstrated to be >96% specific for future RA.  Exposure to PM was assigned using the Environmental Protection Agency Air Quality System and interpolated with inverse distance weighted spatial analyses using Geographic Information Systems.  PM exposures were linked to resident zip codes of FDRs living within 50 km of an air monitoring station in five states.  PM exposures were categorized by tertiles (low, moderate, high levels) due to evidence of nonlinear associations with autoantibodies.  RA-related autoantibody status and PM tertiles were analyzed using nonlinear mixed models to account for repeated measures.

Results:   Our study population had a mean age of 45 years, was 70% female, 72% non-Hispanic White, and mostly non-smokers (88%).  A majority of our study population lived in Colorado (39.1%) followed by California (29.4%), Nebraska (12.6%), Washington (10.6%), and New York (8.3%).  No significant associations were observed between RA-related autoantibody outcomes and PM 2.5 or PM10 tertiles (Table).

Conclusion:   These results suggest that exposure to PM is not significantly associated with autoantibody positivity in individuals without RA, although there is a trend towards an inverse association between PM and the High Risk Profile, which is contrary to our a priori hypothesis that PM is associated with increased risk of RA-related autoimmunity.  The observed results could be due to the aggregate nature of our exposure variable.  Alternatively, exposure to PM may not be an initial trigger of autoimmunity but may act later to facilitate the development of clinically-apparent RA.  Continued observation of this cohort is important to investigate the exact role of air pollution in the etiology of RA.