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. The gene discussed is CD40; the disease is rheumatoid arthritis.