Genome-wide DNA methylation patterns in monocytes derived from patients with primary Sjogren syndrome

Background:Epigenetics,especially DNA methylation,plays an important role in the pathogenesis of primary Sjogren syndrome(pSS).Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients.Methods:A total of 11 pSS patients and five age-matched healthy controls(HCs)were included in this study.Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads.DNA methylation profiles were generated using Human Methylation 850K BeadChips.Results:In monocytes from pSS patients,we identified 2819 differentially methylated positions(DMPs),comprising 1977 hypomethylated-and 842 hypermethylated-DMPs,corresponding to 1313 unique genes when compared with HCs.IFI44L,MX1,PAARP9,and IFITM1,which influence the interferon(IFN)signaling pathway,were among the genes hypomethylated in pSS.Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding,transcriptional regulation,cell adhesion,IFN-g pathway,type I IFN pathway,antigen presentation,Epstein-Barr virus infection,human T-lymphotropic virus type 1 virus infection,and metabolic disease-related pathways.In addition,patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways.Upon comparing monocytes with salivary gland epithelial cells,an important overlap was observed in the cell cycle,cell senescence,and interleukin-17 signaling pathways.The differentially methylated genes were more enriched in the ribosome-and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients.Conclusion:Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.