Background/PurposeSj & ouml;gren's syndrome (SS) is a chronic systemic autoimmune
disease characterized by lymphocytic infiltration and formation of lymphoepithelial
lesions (LEL) in exocrine glands, leading to secretory dysfunction. DNA methylation,
a dynamically regulated epigenetic mark, has been increasingly recognized as a key
regulatory mechanism in the pathogenesis of autoimmune diseases including SS, and
holds promise for identifying novel diagnostic and therapeutic strategies.MethodsReduced
representation bisulfite sequencing (RRBS) was performed on 4 cases of SS and 3 controls
to profile genome-wide DNA methylation patterns. Differentially methylated regions
(DMRs) and associated differentially methylated genes (DMGs) were detected, followed
by functional enrichment analysis. Integration with transcriptomic data (GSE40611)
was performed to identify overlapping epigenetic and transcriptional changes.ResultsA
total of 29,462 DMRs were detected, with 24,116 hypermethylated and 5,346 hypomethylated
regions, indicating an overall increase in methylation levels of SS, and DMGs located
in gene promoter regions were significantly enriched in pathways related to immune
response, transcriptional regulation, and inflammation. Nine hub genes (LCP2, BTK,
LAPTM5, ARHGAP9, IKZF1, WDFY4, CSF2RB, ARHGAP25, DOCK8) were identified, which displayed
promoter hyper-or hypomethylation, indicating the complex epigenetic regulatory mechanisms.ConclusionThis
study reveals extensive DNA methylation alterations in SS, providing new insights
into the epigenetic mechanisms underlying pathogenesis. Moreover, these findings suggest
potential biomarkers or therapeutic targets for further investigation to elucidate
detailed molecular mechanisms of SS.
