Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients

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

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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 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.

Original languageEnglish
Article number17418
Number of pages10
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 27 Nov 2018

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Relapsing-Remitting Multiple Sclerosis
DNA Methylation
Multiple Sclerosis
B-Lymphocytes
Genome
Epigenomics
Lymphotoxin-alpha
Therapeutics
Cell- and Tissue-Based Therapy
Neurodegenerative Diseases
Genes
Central Nervous System
T-Lymphocytes
Research

Cite this

Maltby, V. E., Lea, R. A., Graves, M. C., Sanders, K. A., Benton, M. C., Tajouri, L., ... Lechner-Scott, J. (2018). Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients. Scientific Reports, 8(1), [17418]. https://doi.org/10.1038/s41598-018-35603-0
Maltby, Vicki E. ; Lea, Rodney A. ; Graves, Moira C. ; Sanders, Katherine A. ; Benton, Miles C. ; Tajouri, Lotti ; Scott, Rodney J. ; Lechner-Scott, Jeannette. / Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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 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.",
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Maltby, VE, Lea, RA, Graves, MC, Sanders, KA, Benton, MC, Tajouri, L, Scott, RJ & Lechner-Scott, J 2018, 'Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients' Scientific Reports, vol. 8, no. 1, 17418. https://doi.org/10.1038/s41598-018-35603-0

Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients. / Maltby, Vicki E.; Lea, Rodney A.; Graves, Moira C.; Sanders, Katherine A.; Benton, Miles C.; Tajouri, Lotti; Scott, Rodney J.; Lechner-Scott, Jeannette.

In: Scientific Reports, Vol. 8, No. 1, 17418, 27.11.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lea, Rodney A.

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AU - Benton, Miles C.

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AU - Lechner-Scott, Jeannette

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