Occupational inhalable agents constitute major risk factors for rheumatoid arthritis, particularly in the context of genetic predisposition and smoking

ObjectivesTo assess the effects of occupational inhalable exposures on rheumatoid arthritis (RA) development and their interactions with smoking and RA-risk genes, stratifying by presence of anticitrullinated protein antibodies (ACPA). MethodsData came from the Swedish Epidemiological Investigation of RA, consisting of 4033 incident RA cases and 6485 matched controls. Occupational histories were retrieved, combining with a Swedish national job-exposure matrix, to estimate exposure to 32 inhalable agents. Genetic data were used to define Genetic Risk Score (GRS) or carrying any copy of human leucocyte antigen class II shared epitope (HLA-SE) alleles. Associations were identified with unconditional logistical regression models. Attributable proportion due to interaction was estimated to evaluate presence of interaction. ResultsExposure to any occupational inhalable agents was associated with increased risk for ACPA-positive RA (OR 1.25, 95% CI 1.12 to 1.38). The risk increased as number of exposed agents increased (P-trend<0.001) or duration of exposure elongated (P-trend<0.001). When jointly considering exposure to any occupational inhalable agents, smoking and high GRS, a markedly elevated risk for ACPA-positive RA was observed among the triple-exposed group compared with those not exposed to any (OR 18.22, 95% CI 11.77 to 28.19). Significant interactions were found between occupational inhalable agents and smoking/genetic factors (high GRS or HLA-SE) in ACPA-positive RA. ConclusionsOccupational inhalable agents could act as important environmental triggers in RA development and interact with smoking and RA-risk genes leading to excessive risk for ACPA-positive RA. Future studies are warranted to assess preventive strategies aimed at reducing occupational hazards and smoking, especially among those who are genetically vulnerable.

Automated summary

This study examined the effects of occupational inhalable exposures on the development of rheumatoid arthritis (RA) and their interactions with smoking and RA-risk genes, specifically in relation to the presence of anticitrullinated protein antibodies (ACPA). The results showed that exposure to any occupational inhalable agents was associated with an increased risk for ACPA-positive RA. Furthermore, there was a significantly elevated risk for ACPA-positive RA among individuals who were exposed to occupational inhalable agents, smoked, and had a high genetic risk score (GRS). Significant interactions were found between occupational inhalable agents and smoking/genetic factors (high GRS or HLA-SE) in ACPA-positive RA.