Naive CD8br T Cell Affects Epilepsy through Partial Sphingomyelin Mediation: A Mendelian Randomization Study

Background Several studies have suggested a potential link between immune cells and epilepsy. Nonetheless, the precise causal relationship between immune cells and epilepsy, and the role of metabolites as potential mediators, remain ambiguous. Methods We extracted information on immune cells, metabolites and epilepsy from pooled data from a large-scale genome-wide association study (GWAS). We used Mendelian randomization (MR) analyses to elucidate causal links between immune cells, metabolites and epilepsy. The main statistical method used was inverse variance weighting (IVW). In addition, we investigated the potential mediating role of metabolites in the pathway from immune cells to epilepsy. Finally, we applied bioinformatics methods for validation. Results In assessing the genetic susceptibility of immune cells to epilepsy, we observed 12 positive associations. However, when analyzed in reverse, we found two of these associations to be negative. Similarly, we found 60 positive and 8 negative associations between metabolites and epilepsy. Subsequently, mediation analysis revealed that Naive CD8br T cells affect epilepsy through Partial Sphingomyelin as a mediator. Finally, the bioinformatics analysis revealed alterations in the immune microenvironment between healthy individuals and patients with epilepsy, with notable changes in the differentiation of Naive CD8 T cells. Conclusion There exists a causal association between immune cells, and metabolites with epilepsy, wherein metabolites serve as mediators in the pathway from immune cells to epilepsy.