Circulating immune cells and risk of multiple sclerosis: A Mendelian randomization analysis

Multiple sclerosis (MS) represents a significant global public health concern. Risk factors for MS include autoimmune diseases and immune cell dysfunctions. Immune cells, particularly T cells, B cells, and monocytes, play pivotal roles in the pathogenesis of MS. Nevertheless, the direct causal relationship between these immune cells and MS remains unclear. Genome-wide association studies (GWAS) and Mendelian randomization (MR) offer promising avenues for elucidating genetic susceptibilities and causal relationships between immune cell traits and MS risk. In this study, we employed a 2-sample MR approach to investigate the probable causal connection between immune cells and MS. Immune characteristics, including median fluorescence intensity, relative counts, absolute counts, and mean percentages, were determined using published GWAS data and public resources from the integrative epidemiology unit Open GWAS database. The primary analysis method for MR was inverse variance weighted. Additionally, sensitivity analyses were conducted to validate the robustness of our findings. In this study, we identified that 4 immune traits among 2 immune profiles (relative cell and median fluorescence intensity) demonstrated a significant causal association with MS, including CD27 on IgD- CD38dim B cell (PFDR = 2.81 × 10-3), CD27 on memory B cell (PFDR = .024), CD3 on human leukocyte antigen DR+ CD4+ T cell (PFDR = .031), and CD28 on CD28+ CD45RA+ CD8+ T cell (PFDR = .049). The reverse MR analysis showed that MS did not have significant effects on these immunophenotypes (P > .05). Sensitivity analyses confirmed the robustness of the results (P > .05). Our study has provided evidence indicating a causal relationship between immune cells and MS, which provided new ideas and therapeutic targets for the study of immune mechanism of MS.