DNA methylation changes in CD4+ T cells isolated from multiple sclerosis patients on dimethyl fumarate

Vicki E Maltby; Rodney A Lea; Karen A Ribbons; Katherine A Sanders; Daniel Kennedy; Myintzu Min; Rodney J Scott; Jeannette Lechner-Scott

doi:10.1177/2055217318787826

DNA methylation changes in CD4⁺ T cells isolated from multiple sclerosis patients on dimethyl fumarate

Mult Scler J Exp Transl Clin. 2018 Jul 17;4(3):2055217318787826. doi: 10.1177/2055217318787826. eCollection 2018 Jul-Sep.

Authors

Vicki E Maltby^{1

2}, Rodney A Lea^{2

3}, Karen A Ribbons^{2

4}, Katherine A Sanders⁵, Daniel Kennedy⁶, Myintzu Min^{2

4}, Rodney J Scott^{2

7

8}, Jeannette Lechner-Scott^{1

2

4}

Affiliations

¹ School of Medicine and Public Health, University of Newcastle, Australia.
² Brain and Mental Health, Hunter Medical Research Institute, Australia.
³ Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
⁴ Department of Neurology, John Hunter Hospital, Australia.
⁵ Faculty of Health Sciences and Medicine, Bond University, Australia.
⁶ ARC Centre of Excellence for the Mathematical and Statistical Frontiers, Queensland University of Technology, Brisbane, Australia.
⁷ School of Biomedical Sciences and Pharmacy, University of Newcastle, Australia.
⁸ Department of Medical Genetics, John Hunter Hospital, Australia.

Abstract

Background: Dimethyl fumarate is an oral treatment for multiple sclerosis, whose mechanism of action is not fully understood.

Objective: To investigate the effects of dimethyl fumarate on DNA methylation in the CD4⁺ T cells of multiple sclerosis patients.

Methods: We performed Illumina EPIC arrays to investigate the DNA methylation profiles of CD4⁺ T cells derived from multiple sclerosis patients before and after dimethyl fumarate treatment.

Results: Treatment with dimethyl fumarate resulted in 97% of differentially methylated positions showing hypermethylation. Four genes, SNORD1A, SHTN1, MZB1 and TNF had a differentially methylated region located within the transcriptional start site.

Conclusion: This study investigates the effect of dimethyl fumarate on DNA methylation in multiple sclerosis patients.

Keywords: CD4+ T cells; DNA methylation; Multiple sclerosis; dimethyl fumarate; immunology; relapsing–remitting; tumour necrosis factor.