Impact of Immune Cells on Stroke Limited to Specific Subtypes: Evidence from Mendelian Randomization Study

Stroke is one of the common diseases that pose a severe threat to human health, with immune cells playing a crucial role in its onset and recovery. However, the specific mechanisms and causal relationships of different immune cell groups in various clinical stroke subtypes are unclear. This study explored the causal relationship between immune cells and stroke and its subtypes using Mendelian randomization (MR) analysis.

Data from genome-wide association studies were analyzed using inverse-variance weighted (IVW), MR-Egger, and weighted median methods for MR analysis, along with heterogeneity tests, sensitivity analysis, and pleiotropy analysis.

CD45RA⁺CD28⁻CD8⁺ T cell %T cell (OR 1.002, 95% CI 1.001–1.003; P_FDR = 0.02), CD27 on CD24⁺CD27⁺ B cell (OR 1.127, 95% CI 1.061–1.198; P_FDR = 0.04), CD27 on IgD⁻CD38^dim B cell (OR 1.138, 95% CI 1.076–1.203; P_FDR = 0.005), and CD27 on switched memory B cell (OR 1.144, 95% CI 1.076–1.216; P_FDR = 0.01) were found to increase the risk of large artery stroke. Switched memory B cell %lymphocyte (OR 1.206, 95% CI 1.103–1.318; P_FDR = 0.02) increased the risk of small vessel stroke. Reverse MR analysis did not reveal any reverse causal associations. Furthermore, by substituting the outcome data, a secondary MR analysis was conducted to validate the primary findings.

Our study reveals several causal links between immune phenotypes and stroke and its different subtypes, highlighting the complex interactions between the immune system and stroke. These findings provide new directions for further uncovering the biological basis of stroke and assist in advancing research on early interventions and treatment strategies.