Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Maltby, Vicki; Lea, Rodney; Graves, Moira; Sanders, Katherine; Benton, Miles; Tajouri, Lotti; Scott, Rodney; Lechner-Scott, Jeannette
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 10
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-35603-0
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. The inflammatory process in MS is driven by both T and B cells and current therapies are targeted to each of these cell types. Epigenetic mechanisms may provide a valuable link between genes and environment. DNA methylation is the best studied epigenetic mechanism and is recognized as a potential contributor to MS risk. The objective of this study was to identify DNA methylation changes associated with MS in CD19+ B-cells. We performed an epigenome-wide association analysis of DNA methylation in the CD19+ B-cells from 24 patients with relapsing-remitting MS on various treatments and 24 healthy controls using Illumina 450 K arrays. A large differentially methylated region (DMR) was observed at the lymphotoxin alpha (LTA ) locus. This region was hypermethylated and contains 19 differentially methylated positions (DMPs) spanning 860 bp, all of which are located within the transcriptional start site. We also observed smaller DMRs at 4 MS-associated genes:SLC44A2, LTBR, CARD11 andCXCR5 . These preliminary findings suggest that B-cell specific DNA-methylation may be associated with MS risk or response to therapy, specifically at theLTA locus. Development of B-cell specific epigenetic therapies is an attractive new avenue of research in MS treatment. Further studies are now required to validate these findings and understand their functional significance.