Table 2.
Compilation of studies regarding Sjögren’s syndrome and DNA methylation in cells.
| Country Reference |
Study design for DNA methylation | Cell types | Main outcomes for DNA methylation |
|---|---|---|---|
| Norway BrækkeNorheim K et al. (76) |
Methylation analysis of patients in pSS patients with high or low fatigue | Whole blood | 251 differentially methylated CpG sites were associated with fatigue. The CpG site with the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene. The most distinct hypermethylation was observed at a CpG site annotated to the lymphotoxin alpha gene. |
| France Thabet Y et al. (66) |
Methylation analysis and transcript levels of DNMTs in patients with and without SS | Peripheral B and T cells; SGECs | Global demethylation and reduction in DNMT1 transcript levels in SGECs of SS patients. No differences in methylation profile for B and T cells. |
| France Gestermann N et al. (105) |
Methylation analysis of IRF5 promoter region to determine if this could be the cause for increased IRF5 mRNA expression in patients with SS | Peripheral B and T cells | DNA methylation profile of T CD4+ and B lymphocytes did not differ between SS patients and controls. |
| France Miceli-Richard C et al. (75) |
Methylation comparison in profiles in the CD4+ T cells and CD19+ B cells of pSS patients and controls | CD19+ B cells | 55% of genes had hypermethylated CpG sites, 38% had hypomethylated CpG sites, and the remaining 7% of genes exhibited a mixed methylation pattern at CpG sites in CD19+ B cells. Genes with significantly different DNA methylation patterns are involved in functional pathways required for inflammation. |
| China Yu X et al. (68) |
Methylation analysis of FOXP3 promoter region to determine whether the FOXP3 promoter is hypermethylated and whether aberrant FOXP3 expression occurs in CD4+ T cells from patients with pSS | CD4+ T cells | Hypermethylation at the promoter of FOXP3 in CD4+T cells of pSS patients. A decrease in expression in protein FOXP3 mRNA and protein in CD4+T cells of pSS patients. |
| China Yin H et al. (107) |
Methylation analysis of TNFSF7 promoter region | CD4+ T cells | Hypermethylation at the promoter of TNFSF7 in pSS CD4+T cells. Demethylation of the CD70 promoter regulatory elements contributes to CD70 overexpression in pSS CD4+ T cells and may contribute to autoreactivity. |
| France Belkhir R et al. (108) |
methylation analysis of CD40L promoter region |
CD4+ T cell | No significant differences in methylation profiles between patients and controls. |
| Greece Mavragani CP et al. (109) |
Methylation analysis of LINE-1; expression analysis of DNMT1, DNMT3A, DNMT3B, MeCP2 in SS patients and controls | SGECs | ↑ levels of DNMT1, DNMT3B and MeCP2 transcripts in SS patients. |
| France Konsta OD et al. (110) |
Methylation analysis at SSB promoter region in patients with pSS and cell cultures | SGECs | ↓ global DNA methylation levels in patients with SS. ↓ global methylation associated with lymphocyte infiltration in MiSG; ↓ global methylation associated with anti-La/SSB positive SS cases demethylation at SSB promoter caused higher levels of transcripts and SSB super expression in 5-Aza-C-treated HSG cells. |
| France Konsta OD et al. (111) |
Methylation analysis of the KRT19 locus to investigate epigenetic regulation of expression in patients with SS | SGECs | ↓ global DNA methylation in pSS patients is associated with demethylation of the KRT19 locus as well as with overexpression of the KRT19 protein. |
| USA Chi C et al. (112) |
Methylation analysis in patients with and without SS | SGECs | 215 DMRs in SS patients: 169 hypermethylated regions related to nervous system development, cell signaling and transport; and 46 hypomethylated regions related to immune function. |
| USA Cole MB et al. (113) |
Methylation analysis in patients with varying phenotypes of SS | SGECs | 7,820 DMPs associated with disease status (5,699 hypomethylated and 2,121 hypermethylated DMPs); 57 of the genes with DMPs are involved with the immune response; extensive hypomethylated region near genes PSMB8 and TAP1. |
| Chile Sepúlveda D et al. (114) |
Methylation and expression analysis in genes of the IRE1α/XBP-1 pathway in SS and control patients | SGECs | Hypermethylation in IRE1α, XBP-1 and GRP78 promoter region and diminished transcript levels; ↓ protein levels for IRE1α, XBP-1s and GRP78 in SS patients. |
SS, Sjögren’s syndrome; pSS, Primary Sjögren’s syndrome; SGECs, salivary gland epithelial cells; CpG sites, cytosine guanine dinucleotide (CpG) sites; DNMTs, DNA methyltransferase 1; MiSG, minor salivary gland; FOXP3, fork head Box Protein 3; LINE-1, long interspersed repeat element 1; anti, SSB, anti-Sjögren’s syndrome antigen B; HSG, human salivary gland; KRT19, keratin 19; DMRs, Differentially methylated regions; DMPs, differentially methylated positions; IRE1α, inositol-requiring enzyme 1alpha; XBP-1s, X-box binding protein 1s; GRP78, glucose-regulating protein 78.