Background Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with incompletely understood etiology. Very little is known about the role of epigenetic dysregulation in the pathogenesis of pSS. Recently, Global DNA methylation profiles have been gradually surfaced to the ground, however, there are not studies in terms of global DNA methylation alterations in the pSS. We hypothesize that there DNA methylation profiles in pSS, which may be identified using higher resolution assay methods.
Objectives Objectives: To investigate Global DNA methylation profiles of SS patients.
Methods We used the newly developed illumina HumanMethylation 450 BeadChip in the blood of 3 Sjogren syndrome and 3 healthy controls and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in pSS development and progression. We also confirmed our methylation results in an independent data set. Two aberrant
DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues.
Results A total of 472139 CpG sites showed significant differences in DNA methylation (FDR adjusted P,0.05), defined as a mean methylation
difference of at least 20% between PCa and normal samples. Furthermore, a total of 122 genes had more than one differentially methylated CpG site in their promoter region and a gene expression pattern that was inverse to the direction
of change in DNA methylation (e.g. decreased expression with increased methylation, and vice-versa).Pathway analsis reveals methylation difference in MAPK signaling, Wnt signaling, p53 signaling, Calcium signaling,Chemokine signaling, Antigen processing and presentation, B cell receptor,T cell receptor signaling, Salivary secretion, VEGF signaling, TGF-beta signaling Toll-like receptor signaling and Jak-STAT signaling pathway Other relevant genes such as CD247, TNFRSF25, PTPRC, GSTM1 and PDCD1 were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18 and IFITM1.
Conclusions Conclusion: This is the first epigenome-wide DNA methylation study in pSS. Our data highlight a role for DNA methylation in pSS and identify disease-associated DNA methylation changes in several genes and pathways in naïve CD4+ T cells in pSS that may be involved in the pathogenesis of this disease.
Disclosure of Interest : None declared
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