Epigenetic landscape of IL-10 in graves’ disease: site-specific DNA methylation alterations and their associations with immune dysregulation

Epigenetic modifications, particularly deoxyribonucleic acid (DNA) methylation, regulate the expression of immune-mediated factors. This study aimed to investigate the methylation landscape of the interleukin-10 (IL10) gene in Graves' disease (GD). This study quantitatively profiled DNA methylation levels within the IL-10 gene using peripheral blood samples from GD patients and healthy controls. Machine learning models were constructed based on CpG methylation features to classify disease status. Furthermore, correlation between specific CpG sites methylation and clinical indicators were analyzed. This study enrolled 60 patients diagnosed with GD and 51 healthy controls. Methylation analysis revealed significantly elevated methylation at multiple IL-10 CpG sites in the GD group compared to the healthy controls (p < 0.01), forming a hypermethylated cluster. Interestingly, the newly-diagnosed GD (NGD) group also showed higher methylation at specific sites compared to the recurrent GD (RGD) group. Correlation analysis showed that methylation at chr1_206947188_R and chr1_206947135_R were positively correlated with FT3 and TRAb levels, indicating that site-specific methylation changes were associated with disease severity and immune activity in GD. Our findings highlight distinct methylation patterns of the IL-10 gene in GD, with specific CpG sites carrying potential implications for disease diagnosis, stratification, and monitoring.