Causal effects of immune cell phenotypes on the risk of autoimmune liver diseases: a bidirectional two-sample Mendelian randomization study.

Background: Currently, the relationship between immune cell phenotypes and susceptibility to autoimmune liver diseases (AILDs) remains underexplored. This study aims to investigate potential causal associations between immune cell phenotypes and AILDs using a bioinformatics approach. Methods: We utilized a two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cell phenotypes and susceptibility to AILDs, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The data of 731 immune cell phenotypes were sourced from a study cohort with 3,757 individuals, while all AILDs summary data were obtained from an open-access database containing the data of AIH, PBC and PSC from 485,234, 24,510 and 14,890 subjects, respectively. Results: For AIH, its incidence was negatively influenced by three phenotypes of natural killer (NK) cells [HLA-DR+ NK absolute count (AC), HLA-DR+ NK %NK, and HLA-DR+ NK %CD3- lymphocyte] and two phenotypes of monocytes (CD14+ CD16+ monocyte AC, CD16 on CD14- CD16+ monocyte), as well as positively affected by HLA-DR on plasmacytoid dendritic cell (DC) and HLA-DR on CD33- HLA-DR+ myeloid cell. For PBC, its susceptibility was positively impacted by three phenotypes of B cells, i.e., CD27 on CD24+ CD27+ B cell, CD27 on IgD+ CD38- unswitched memory (unsw mem) B cell, and CD27 on memory B cell. For PSC, its risk was negatively correlated with CD28 on CD45RA- CD4 not regulatory T (Treg) cell and FSC-A on CD4+ NK cell. Conclusions: This study suggests a potential causal relationship between immune cells and AILDs, providing preliminary insights into their immunological basis and informing the potential therapeutic targets for further functional studies in treating AILDs.