The causal relationship between immune cells and rheumatoid arthritis: A dual sample Mendelian randomization study

The etiology of rheumatoid arthritis (RA) is still unclear, but it has been shown to be genetically related. While previous studies have shown a causal relationship between immune cells and RA, there has been no systematic evaluation of the causal relationship between immune cell characteristics and RA in terms of genetic variation. For this study, a comprehensive Mendelian randomization analysis was performed to determine the causal relationship between immune cell characteristics and RA. On the basis of publicly available genetic data, we examined the causal relationship between 731 immune cell characteristics and the risk of RA. In addition to 118 absolute cell (AC) counts, 389 median fluorescence intensities reflecting surface antigen levels, and 32 morphologic parameters, 192 relative counts were collected. We validated the robustness, heterogeneity, and horizontal pleiotropy of our results by carrying out comprehensive sensitivity analyses. False discovery rate-corrected, 12 immune cell phenotypes had a causal effect on RA, and the ratio of ratios for risk of RA using the inverse variance weighting method IgD-CD27-B cell % B cell, CD27 on memory B cell, CD27 on IgD-CD38dim, and CD27 on IgD-% of CD27-lymphocyte. In the TBNK group, HLA DR + NK%CD3-lymphocyte. In the Treg panel, CD28 on resting Treg, while in the cDC panel, CD86 + myeloid DC %DC, CD62L-DC %DC, CD62L-CD86 + myeloid DC %DC, CD86 + myeloid DC AC, CD62L-CD86 + myeloid DC AC, and HLA DR on plasmacytoid DC. There was a causal effect of RA on 2 immune characteristics, including CD38 on plasma blast-plasma cell, and HLA DR on CD33-HLA DR+. Our study demonstrates an intrinsic link between immune cells and RA from a genetic perspective, providing guidance for future clinical studies.