Unveiling the Role of CD27+ Memory B Cells in Primary Biliary Cholangitis: A Mendelian Randomization Study

Abstract

Abstract This study performed a two-sample Mendelian randomization (MR) approach based on genome-wide association study (GWAS) summary statistics to investigate the causal relationship between immune cells and primary biliary cholangitis (PBC). A total of 731 immune cell traits were evaluated for association with PBC to identify diagnostic biomarkers and potential therapeutic targets. GWAS data on immune cell traits and PBC were collected with Single Nucleotide Polymorphisms (SNPs) used as instrumental variables. The IVW model showed a causal relationship between elevated levels of four CD27+ memory B cell types and increased risk of PBC (PFDR < 0.05). Specifically, CD27 expression on CD24+ CD27+ B cells, IgD+ CD24+ B cells, IgD− CD38dim B cells and unswitched memory B cells showed associations with PBC risk. However, no causal relationship between PBC and these immune cell traits was observed in the reverse MR analysis. Differential gene analysis from the Gene Expression Omnibus (GEO) database, Spearman correlation analysis and enrichment analysis further supported the association between CD27+ memory B cells and PBC risk. These findings suggest that CD27 + memory B cells play a role in the pathogenesis of PBC and may serve as important targets for diagnostic and therapy strategies.