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

Research output: Contribution to journalArticleResearchpeer-review

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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.

Original languageEnglish
Article number118
JournalClinical Epigenetics
Volume7
Issue number1
DOIs
Publication statusPublished - 5 Nov 2015

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DNA Fingerprinting
DNA Methylation
Epigenomics
Multiple Sclerosis
Genome
T-Lymphocytes
Methylation
HLA-DRB1 Chains
Relapsing-Remitting Multiple Sclerosis
Genetic Predisposition to Disease
Blood Donors
Case-Control Studies
Genes

Cite this

Maltby, Vicki E. ; Graves, Moira C. ; Lea, Rodney A. ; Benton, Miles C. ; Sanders, Katherine A. ; Tajouri, Lotti ; Scott, Rodney J. ; Lechner-Scott, Jeannette. / Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients. In: Clinical Epigenetics. 2015 ; Vol. 7, No. 1.
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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.",
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Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients. / Maltby, Vicki E.; Graves, Moira C.; Lea, Rodney A.; Benton, Miles C.; Sanders, Katherine A.; Tajouri, Lotti; Scott, Rodney J.; Lechner-Scott, Jeannette.

In: Clinical Epigenetics, Vol. 7, No. 1, 118, 05.11.2015.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Maltby, Vicki E.

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AU - Benton, Miles C.

AU - Sanders, Katherine A.

AU - Tajouri, Lotti

AU - Scott, Rodney J.

AU - Lechner-Scott, Jeannette

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AB - 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.

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