Exploring the association between brominated flame retardant exposure and the risk of rheumatoid arthritis: A...

Brominated flame retardants (BFRs), widely used for their flame-retardant properties, have raised global health concerns. Given the limited evidence linking BFRs to rheumatoid arthritis (RA), we investigated the association between BFR exposure and RA, as well as the role of immune-inflammatory responses. This study recruited 9908 general adults. Serum BFRs, including 8 polybrominated diphenyl ethers (PBDEs) and 2,2',4,4',5,5'-Hexabromobiphenyl (PBB153), were measured to evaluate exposure levels. The pan-immune-inflammation value (PIV) and neutrophil-to-lymphocyte ratio (NLR) were calculated to assess immune-inflammatory response. The logistic regression model and generalized linear model were used to estimate the associations of individual and mixed BFRs with RA and immune-inflammatory indicators. Mediation analyses and toxicogenomic bioinformatics analyses were conducted to explore the underlying mechanism. Specific PBDE congeners (PBDE85, 100, 153, 154, 209) and PBB153 showed significant dose-dependent associations with an increased risk of RA (all P trend<0.05). Doubling the concentration increases in these compounds elevated RA risk by 10 %-21 %. Mixed BFR exposure also significantly increased the risk of RA, with PBB153 showing the highest contribution weight. PBDE85 and PBDE154 were positively associated with increased PIV or NLR in a dose-response manner (P and P trend<0.05). PIV or NLR partially mediated the associations of PBDE85 and PBDE154 with RA risk. The toxicogenomic bioinformatics analyses further indicated the important role of regulation of immune-inflammatory response in linking BFR exposure to RA. Overall, BFR exposure was associated with an increased risk of RA, and immune-inflammatory responses may contribute to the pathogenesis of BFR-associated RA.