Identification of a shared PAX5-mediated B-cell regulatory axis in inflammatory bowel disease and rheumatoid arthritis

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disease characterized by intestinal inflammation. Rheumatoid arthritis (RA) can occur concurrently with IBD as a comorbidity. However, the common dysregulated node underlying both IBD and RA remains largely unexplored. We screened differentially expressed genes (DEGs) in IBD and RA datasets from the Gene Expression Omnibus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for functional enrichment. Hub genes were identified by constructing a protein–protein interaction (PPI) network. We further identified transcription factors regulating the hub genes and validated the expression of the hub genes and the corresponding transcription factors in additional IBD and RA datasets. Finally, the transcription factor PAX5 was validated in IBD and RA tissues using multiplex immunohistochemistry (mIHC). A total of 54 common DEGs were shared between IBD and RA. GO analysis indicated that these genes were significantly enriched in immune response activation. KEGG analysis suggested that these genes may be involved in cytokine–cytokine receptor interaction. PPI network analysis identified 10 hub genes. Among the transcription factors regulating these hub genes, PAX5 was found to regulate CD19 and CD79A. PAX5 was identified as a prioritized candidate shared regulatory node linking IBD and RA. These findings were further supported by mIHC. Our integrated analysis identified PAX5 as a prioritized candidate linking IBD and RA through B-cell-associated pathways, suggesting its potential as a biomarker and therapeutic target that warrants further investigation.