Immunoglobulin Heavy Constant Mu as a Shared Gene in Periodontitis and Rheumatoid Arthritis: A Bioinformatic Analysis

Rheumatoid arthritis (RA) and periodontitis (PD) are two inflammatory diseases sharing immunopathogenic features and a common inflammatory environment. This exploratory bioinformatic study aimed to generate hypotheses regarding shared genes between PD and RA.

Gene expression omnibus (GEO) datasets for PD and RA were utilized. Weighted gene coexpression network analysis (WGCNA) was conducted to identify modules associated with PD and RA. Differential gene expression analysis was performed to find DEGs, followed by functional enrichment analysis using 'clusterProfiler'. Machine learning models were applied to screen target genes. Immunoglobulin Heavy Constant Mu (IGHM) expression in clinical blood samples was validated using RT-qPCR and ELISA.

By intersecting WGCNA module genes with upregulated DEGs, we identified 17 candidate genes for PD and 37 for RA. Three machine learning models (RF, SVM, and GLM) were further applied to screen these candidates. The intersection of the PD and RA candidate genes identified IGHM as a potential shared gene. Notably, both IGHM mRNA and protein exhibited high expression levels in clinical blood samples from patients diagnosed with PD and RA. ROC curve analysis demonstrated that IGHM had potential diagnostic value for PD and RA. GSEA revealed that IGHM was associated with B cell receptor, Th cell differentiation, and NF-kappa B signalling pathways in both diseases. Expression levels of two TFs IRF4 and BHLHE41 were significantly positively correlated with IGHM in both PD and RA. Immune infiltration analysis showed that the adaptive immunity level was significantly higher, innate immunity level lower, and T cell response level lower in high IGHM group compared to low IGHM expression group in both PD and RA.

IGHM may serve as a potential shared gene of PD and RA and may have potential as a general surrogate plasma/B-cell marker reflecting immune responses in both diseases.