Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients

Vicki E Maltby; Moira C Graves; Rodney A Lea; Miles C Benton; Katherine A Sanders; Lotti Tajouri; Rodney J Scott; Jeannette Lechner-Scott

doi:10.1186/s13148-015-0152-7

Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients

Clin Epigenetics. 2015 Nov 5:7:118. doi: 10.1186/s13148-015-0152-7. eCollection 2015.

Authors

Vicki E Maltby^#^{1

2}, Moira C Graves^#^{1

3}, Rodney A Lea^{1

4}, Miles C Benton⁴, Katherine A Sanders^{1

5}, Lotti Tajouri⁵, Rodney J Scott^{1

6}, Jeannette Lechner-Scott^{1

3

7}

Affiliations

¹ Centre for Information Based Medicine, Hunter Medical Research Institute, Newcastle, Australia.
² School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
³ School of Medicine and Public Health, Univeristy of Newcastle, Newcastle, Australia.
⁴ Insitute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
⁵ Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia.
⁶ Division of Molecular Medicine, Pathology North, Newcastle, Australia.
⁷ Department of Neurology, Devision of Medicine, John Hunter Hospital, Newcastle, Australia.

^# Contributed equally.

Abstract

Background: Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. In this study we aim to identify DNA methylation changes associated with MS in CD8+ T cells in 30 relapsing remitting MS patients and 28 healthy blood donors using Illumina 450K methylation arrays.

Findings: Seventy-nine differentially methylated CpGs were associated with MS. The methylation profile of CD8+ T cells was distinctive from our previously published data on CD4+ T cells in the same cohort. Most notably, there was no major CpG effect at the MS risk gene HLA-DRB1 locus in the CD8+ T cells.

Conclusion: CD8+ T cells and CD4+ T cells have distinct DNA methylation profiles. This case-control study highlights the importance of distinctive cell subtypes when investigating epigenetic changes in MS and other complex diseases.

Keywords: CD8+ T cells; DNA methylation; HLA-DRB1; Multiple sclerosis.