Causal association between immune cells and sepsis: a based on Mendelian randomization method study

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To investigate the causal association between immune cell and different types of sepsis by using Mendelian randomization (MR) method, and to find the immune cell phenotypes causally associated with sepsis. Summary data for various circulating immune cell phenotypes were obtained from the GWAS catalog (GCST90001391-GCST90002121). Sepsis data were sourced from the UK Biobank database. Single nucleotide polymorphisms (SNP) were used as instrumental variables. The correlation threshold of P < 5×10-6 was used to identify the strongly correlated instrumental variables, and the code was used to remove the linkage disequilibrium and the instrumental variables with F-value < 10. Inverse variance weighting (IVW) was used as the main research method to evaluate the stability and reliability of the results, including Cochran's Q test, MR-Egger regression and Leave one out. Reverse MR analysis was performed based on the immunophenotypic results of the removal of horizontal pleiotropy, and the immune cell phenotype with one-way causal association was obtained. Odds ratio (OR) and 95% confidence interval (95%CI) were used to represent the effect value of the results. CD16 on CD14-CD16+; monocyte had horizontal pleiotropy in sepsis (OR = 0.965 4, 95%CI was 0.933 5-0.998 3, P = 0.039 6). There were five immunophenotypes that had reverse causal associations with the types associated with sepsis. After excluding immune cell phenotypes with horizontal pleiotropy and reverse causation, a total of 42 immune cell phenotypes with sepsis, 36 immune cell phenotypes with sepsis (28-day death in critical care), 32 immune cell phenotypes with sepsis (critical care), 44 immune cell phenotypes with sepsis (28-day death), and 30 immune cell phenotypes had potential causal associations with sepsis (under 75 years old). After false discovery rate (FDR) correction, the correlations between BAFF-R on IgD- CD38br and sepsis (28-day death) were negative and strong (OR = 0.737 8, 95%CI was 0.635 9-0.856 0, P = 6.05×10-5, PFDR = 0.044 2). A variety of immune cell phenotypes may have a protective effect on sepsis, especially BAFF-R on IgD- CD38br expression is negatively correlated with sepsis (28-day death), which provides a new idea for immune modulation therapy in sepsis.