Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract

Objective: Methylation is known to regulate biological processes and alterations in methylation patterns have been associated with a variety of diseases. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an unexplained disorder associated with immunological and molecular changes. CD4+T cells specifically, regulatory T cells (Tregs) have been implicated in CFS/ME patients where significant increases in Tregs have been observed in these patients. Therefore the objective of this study was to examine methylation in CD4+T cells from CFS/ME patients. Methods: The study comprised twenty-five CFS/ME participants and eighteen controls aged between 25-60 years. A volume of 20 ml whole blood was collected from each participant and peripheral blood mononuclear cells were isolated via density gradient centrifugation. A negative isolation kit was used to isolate the CD4+T cells from the peripheral blood samples. Genome wide methylation studies were performed on isolated CD4+T cells using the Illumina Infinium 450 K Human methylation array system. Data analysis was performed using Genome studio and Partek Enrichment software. Results: 120 CpGs were observed to be differentially methylated in the CFS/ME patients in comparison to the controls. Of these 70 were associated with known genes. The majority of the differential methylated regions in the CFS/ME patients were hypomethylated. Additionally, most of the genes with differentially methylated regions in the CFS/ME patients were responsible for apoptosis, cell development, cell function and metabolic activity. Conclusion: The present study demonstrates that epigenetic changes in CD4+T cells may have a potential role in the immunological changes observed in CFS/ME patients.