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Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD4]

ABSTRACT: Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological processes. To identify DNA methylation hallmarks, associated with MS, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same individuals (relapsing-remitting MS patients and healthy subjects), using Illumina 450K methylation arrays. We revealed significant changes in DNA methylation for both cell populations of studied groups. In CD4+ cells the majority of differentially methylated positions (DMPs) were shown to be hypomethylated, while in CD14+ cells – hypermethylated in MS patients. Noteworthy, in CD4+, but not in CD14+ cells, we found differential methylation of HLA-DRB6 gene from HLA locus, which is known to have the strongest genetic association with MS. Besides, about 20% of DMPs identified in studied cells were identical; they all had the same direction of methylation changes in both cell populations and may be involved in basic epigenetic processes occuring in MS. These findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to MS; further studies are now required to validate these results and understand their functional significance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189255 | GEO | 2022/02/28

REPOSITORIES: GEO

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Project description:Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints involved with genetic and epigenetic aberrant. Recent evidence found more and more importance of the epigenetic contribution, especially the DNA methylation, to the pathogenesis of rheumatoid arthritis. To understand the extent and nature of dysregulated DNA methylation in rheumatoid arthritis T cells, we performed a genome-wide DNA methylation study in CD4+ T cells in 12 rheumatoid arthritis patients compared to 12 matched normal healthy controls. [Methods and Result] Cytosine methylation status was quantified with Illumina methylation 450K microarray (HM450K, 485512 CpG sites). We identified 810 hypomethylated and 392 hypermethylated CG sites in RA CD4+ T cells compared to normal controls, representing 383 and 785 genes hypermethylated and hypomethylated in RA patients (P<3.4*10-7). Cluster analysis based on significantly differential methylated loci showed distinct separation between RA and normal controls. Gene ontology analysis showed alternative splicing (P=1.2*10-7, FDR) and phosphoprotein (1.7*10-2, FDR) were significantly aberrant in RA patients, indicating the abnormal of transcript alternative splicing and protein modification mediated by DNA methylation might play important role in the pathogenesis of rheumatoid arthritis. What’s more, the result showed human leukocyte antigen (HLA) region was frequently hypomethylated in RA patients, including HLA-DRB6, HLA-DQA1 and HLA-E, however, HLA-DQB1 showed different methylation profiles with significant hypermethylation in CpG island region and hypomethylation in CpG shelf region. Outsite of the MHC region, the most hypermethylated genes in RA included HDAC4, NXN, TBCD and TMEM61 while the most significant hypomethylated genes included ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9. [Conclusion] Genome-wide DNA methylation patterns revealed significant DNA methylation change in CD4+ T cells from patients with rheumatoid arthritis. 12 rheumatoid arthritis and 12 matched health individuals

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Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD4]

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