Casual relationship between 731 immunophenotypes and sepsis: A Bidirectional Two-sample mendelian randomization study

Abstract Background The causal relationship between immune cell phenotypes and their interactions with sepsis remains partially understood, with several aspects subject to debate. Our objective was to bidirectionally investigate specific immune cell phenotypes and their association with sepsis. Methods We performed bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) summary statistics to investigate the causal links between 731 immunophenotypes and sepsis. We conducted comprehensive sensitivity analyses to ensure robustness and consistency and assess for possible horizontal pleiotropy of our results. Results The analysis, adjusted for multiple comparisons using the Bonferroni method, revealed that increased levels of CD66b + + myeloid cells (Odds Ratio [OR] = 0.945, 95% Confidence Interval [CI]: 0.916–0.974, P = 0.0002, PBonferroni= 0.0089), BAFF-R on IgD- CD38br B cells (OR = 0.919, 95% CI: 0.873–0.966, P = 0.001, PBonferroni = 0.0365), and CD39 on CD39 + CD8br regulatory T cells (OR = 0.927, 95% CI: 0.890–0.966, P = 0.0003, PBonferroni = 0.0116) play a protective role against sepsis, as determined by the inverse variance weighted (IVW) method. Our findings did not reveal any significant impacts of sepsis on immunophenotypes. Conclusions This study highlights the potential protective roles of CD66b + + myeloid cells, BAFF-R on IgD- CD38br B cells, and CD39 on CD39 + CD8br regulatory T cells against sepsis. These insights advance our understanding of the immune system's interaction with sepsis risk and propose new avenues for immunotherapy-oriented interventions.