Dataset Information

Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression.

ABSTRACT:

Background

Multiple Sclerosis (MS) is a chronic inflammatory disease and a leading cause of progressive neurological disability among young adults. DNA methylation, which intersects genes and environment to control cellular functions on a molecular level, may provide insights into MS pathogenesis.

Methods

We measured DNA methylation in CD4⁺ T cells (n?=?31), CD8⁺ T cells (n?=?28), CD14⁺ monocytes (n =?35) and CD19⁺ B cells (n?=?27) from relapsing-remitting (RRMS), secondary progressive (SPMS) patients and healthy controls (HC) using Infinium HumanMethylation450 arrays. Monocyte (n?=?25) and whole blood (n =?275) cohorts were used for validations.

Findings

B cells from MS patients displayed most significant differentially methylated positions (DMPs), followed by monocytes, while only few DMPs were detected in T cells. We implemented a non-parametric combination framework (omicsNPC) to increase discovery power by combining evidence from all four cell types. Identified shared DMPs co-localized at MS risk loci and clustered into distinct groups. Functional exploration of changes discriminating RRMS and SPMS from HC implicated lymphocyte signaling, T cell activation and migration. SPMS-specific changes, on the other hand, implicated myeloid cell functions and metabolism. Interestingly, neuronal and neurodegenerative genes and pathways were also specifically enriched in the SPMS cluster.

Interpretation

We utilized a statistical framework (omicsNPC) that combines multiple layers of evidence to identify DNA methylation changes that provide new insights into MS pathogenesis in general, and disease progression, in particular. FUND: This work was supported by the Swedish Research Council, Stockholm County Council, AstraZeneca, European Research Council, Karolinska Institutet and Margaretha af Ugglas Foundation.

SUBMITTER: Ewing E

PROVIDER: S-EPMC6558224 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression.

Ewing Ewoud E Kular Lara L Fernandes Sunjay J SJ Karathanasis Nestoras N Lagani Vincenzo V Ruhrmann Sabrina S Tsamardinos Ioannis I Tegner Jesper J Piehl Fredrik F Gomez-Cabrero David D Jagodic Maja M

EBioMedicine 20190430

<h4>Background</h4>Multiple Sclerosis (MS) is a chronic inflammatory disease and a leading cause of progressive neurological disability among young adults. DNA methylation, which intersects genes and environment to control cellular functions on a molecular level, may provide insights into MS pathogenesis.<h4>Methods</h4>We measured DNA methylation in CD4<sup>+</sup> T cells (n = 31), CD8<sup>+</sup> T cells (n = 28), CD14<sup>+</sup> monocytes (n = 35) and CD19<sup>+</sup> B cells (n = 27) from ...[more]

PMID: 31053557

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Dataset Information

Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression.

Background

Methods

Findings

Interpretation

Publications

Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression.

Similar Datasets

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