Resting Treg Cells Mediates the Relationship Between Primary Biliary Cholangitis (PBC) and the Risk of Different Types of Stroke: A Mendelian Randomization Study

Background: Previous clinical studies have shown that primary biliary cholangitis (PBC)-induced hyperlipidemia may lead to an increased risk of stroke. Objectives: We employed Mendelian randomization (MR) to explore the relationship between PBC and stroke and to investigate the mediating factors. Methods: We utilized two-way MR to analyze pooled data from the genome-wide association study (GWAS) of PBC and stroke, aiming to determine a causal link between them. In addition, we employed two-step MR to quantify the proportion of PBC effects on acute ischemic stroke mediated by resting Treg (rTregs) cells. Results: Our study revealed a significant association between PBC and acute ischemic stroke. The PBC increased the risk of acute ischemic stroke [odds ratio (OR), 1.02; 95% confidence interval (CI), 1.00 - 1.05; P = 0.013]. This finding was corroborated by an extensive sensitivity analysis. Genetic prediction revealed that 4.7% of the association between PBC and increased risk of acute ischemic stroke was mediated by rTregs cells. Conclusions: Our findings illustrate that rTregs cells mediate the increased risk of acute ischemic stroke caused by PBC. Additional research is needed to further understand the role and mechanism of rTregs cells in acute ischemic stroke.