Causal relationship between immune cell-mediated circulating inflammatory proteins and rheumatoid arthritis

• Four circulating inflammatory proteins were causally associated with rheumatoid arthritis risk: one risk factor and three protective factors. • Forty-six immune cell phenotypes showed causal associations with rheumatoid arthritis, with 20 as risk factors and 26 as protective factors. • CD19 on IgD- CD38br partially mediated the causal effect of interleukin-18 on rheumatoid arthritis, with a mediation proportion of 5.7%. • Reverse Mendelian randomization found no reverse causation from rheumatoid arthritis to the identified inflammatory proteins.