The role of immune cells in cirrhosis: evidence from a two-sample Mendelian randomization study

Background The burden on social and economic development caused by cirrhosis, a common terminal pathological process in most liver diseases, is substantial. The liver, being the outstanding immune organ in the body, thus emphasizing the critical role of immune cells in the pathogenesis and progression of cirrhosis.However, there is a paucity of studies investigating the correlation between immunophenotype and cirrhosis. The Mendelian randomization(MR) study was employed to explore relationships between these factors, aiming to provide new directions and insights for clinical research. Methods The genetic data associated with cirrhosis from genome-wide association studies (GWAS) were obtained from the FinnGen R10 database.Inverse variance weighting (IVW) completing with MR-Egger, weighted mode, simple mode, and weighted median were adopted to enhance the robustness of our analysis. Finally, the potential association between immunophenotypes and cirrhosis was clarified. Results Fourteen immunophenotypes closely associated with cirrhosis were identified. Specifically, there were four distinct types of B cells, seven distinct types of Myeloid cells, one classical dendritic cell (cDC), CCR2 on CD62L + myeloid DC; one type of Treg cell, CD39 on CD39 + secreting Treg; one type of TBNK cells, SSC-A on NK. The robustness of the MR Study was further confirmed through comprehensive evaluations of pleiotropy and heterogeneity. Conclusion The MR study is the pioneering effort to offer informative and comprehensive data supporting the association between immunophenotypes and cirrhosis. These findings have significant implications for tailoring individualized treatment strategies, optimizing cirrhosis management, and enhancing overall survival.