Integrative single-cell transcriptomics and mendelian randomization identifies BTN3A2 as a shared protective factor in Behçet's disease and inflammatory bowel disease.

Background: Behçet's disease (BD) and inflammatory bowel disease (IBD) are immune-mediated chronic inflammatory disorders. Although they exhibit significant overlap in clinical manifestations and immunological features, whether they share molecular targets and pathogenic links remains unclear. This study aimed to explore the possible linking and shared treatment target between these two diseases. Methods: We analyzed scRNA-seq data from the peripheral blood of BD and IBD patients to delineate the immune cell landscape and identify key subsets via differential proportion analysis. Combining expression quantitative trait loci (eQTL) and genome-wide association study (GWAS) data, Mendelian Randomization (MR) analysis was performed to infer causal relationships between the key gene expressions in BD and IBD. Finally, validation was performed using the experimental autoimmune uveitis (EAU) mouse model, external datasets, and blood samples from BD uveitis patients. Results: scRNA-seq analysis revealed a significant decrease in the proportion of CD4 Conclusions: This study identifies BTN3A2 as a shared protective factor in BD and IBD and provides experimental evidence linking BD-associated ocular inflammation to intestinal pathology, establishing a new basis for comorbidity-targeted therapeutic strategies.