Open AccessSpecific hypomethylation programs underpin B cell activation in early multiple sclerosis
Author(s) -
Qin Ma,
Stacy J. Caillier,
Shaun Ivan Muzic,
AUTHOR_ID,
Michael R. Wilson,
Roland G. Henry,
Stephen L. Hauser,
Alessandro Didonna,
Alessandro Didonna,
Jorge R. Oksenberg
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111920118
Subject(s) - epigenetics , dna methylation , biology , multiple sclerosis , transcriptome , immune system , cd19 , epigenesis , immunology , methylation , genetics , dna , gene , gene expression
Significance Cellular and molecular mediators driving multiple sclerosis (MS) pathology have been discovered to a great extent. However, the early molecular events leading to aberrant immune responses remain largely unknown. In this study, we combined bisulfite sequencing with transcriptome profiling to characterize the epigenetic landscape of four peripheral immune cell populations isolated from newly diagnosed, untreated MS patients and healthy individuals. We demonstrate widespread hypomethylation in CD19+ B cells at clinical disease onset. Notably, this epigenetic signature is functionally linked with the overactivation of B cells. Altogether, our results pinpoint the role of aberrant DNA methylation in connecting defects in the periphery with central nervous system autoimmunity and corroborate the key role of B cells in the initial stages of MS.