- Title
- Genome-wide DNA methylation changes in CD19⁺ B cells from relapsing-remitting multiple sclerosis patients
- Creator
- Maltby, Vicki E.; Lea, Rodney A.; Graves, Moira C.; Sanders, Katherine A.; Benton, Miles C.; Tajouri, Lotti; Scott, Rodney J.; Lechner-Scott, Jeannette
- Relation
- Scientific Reports Vol. 8, no. 17418
- Publisher Link
- http://dx.doi.org/10.1038/s41598-018-35603-0
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2018
- Description
- 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 and CXCR5. These preliminary findings suggest that B-cell specific DNA-methylation may be associated with MS risk or response to therapy, specifically at the LTA 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.
- Subject
- multiple sclerosis; genome-wide DNA; DNA methylation; epigenome-wide association
- Identifier
- http://hdl.handle.net/1959.13/1405729
- Identifier
- uon:35542
- Identifier
- ISSN:2045-2322
- Rights
- © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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