Genetically predicted immune cells and metabolites mediate the causal relationship between inflammatory factors and rheumatoid arthritis

This study investigates the causal relationship between inflammatory factors and rheumatoid arthritis (RA) and potential immune cells and metabolites mediator using Mendelian randomization. A bidirectional Mendelian randomization study was conducted using statistics from a genome-wide association study database to explore the causal relationship between inflammatory factors and RA, combined with mediation analysis, to discover potential immune cells and metabolites with mediating effects, and to estimate the proportion of total effects mediated by each immune cell and metabolite. The level of the inflammatory factor CD40L receptor was positively associated with an elevated risk of RA. Mediation analysis showed evidence of indirect effect of CD40L receptor levels on RA through CD14+CD16- monocyte% monocyte (OR 1.022, 95% CI, 1.003-1.042; P = .021), X-24757 levels (OR 1.168, 95% CI, 1.035-1.317; P = .011) and IgD on IgD + CD38- unswitched memory (OR 1.088, 95% CI, 1.010-1.173; P = .026), with a mediated proportion of 1.89%, 10.6%, and 11.6% of the total effect, respectively. Our study identified the causal relationship between inflammatory factor CD40L receptor levels and RA and the potential mediating role of 2 immune cells and 1 metabolite.