ArticleProceedings of the National Academy of Sciences of the United States of America2021
Specific hypomethylation programs underpin B cell activation in early multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Genes, Gene Loci, and Their Impacts on the Immune System in the Development of Multiple Sclerosis: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Epigenetic regulation of B cell tolerance and dysfunction in autoimmune disease.Nature reviews. Immunology · 2026Review
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Proximity-based proteomic profiling uncovers distinct interactome of human RAG1 and RAG2.Acta biochimica et biophysica Sinica · 2026Article
- FCRL5, a B-Cell Marker With Novel Diagnostic and Prognostic Value for Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Neuroprotective strategies in multiple sclerosis: a status update and emerging paradigms.Expert review of neurotherapeutics · 2025Review
- T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis.Cell reports. Medicine · 2025Article
- Reduced CD40 expression in B cell subsets of individuals with radiologically isolated syndrome.Frontiers in immunology · 2025Article
- Genome-wide Methylation Dynamics and Context-dependent Gene Expression Variability in Differentiating Preadipocytes.Journal of the Endocrine Society · 2024Article
- The lung-brain axis in multiple sclerosis: Mechanistic insights and future directions.Brain, behavior, & immunity - health · 2024Article
- Myelin-reactive B cells exacerbate CD4Nature communications · 2024Article
- The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis.Journal of immunology research · 2024Review
- Quantification of Autoreactive Antibodies in Mice upon Experimental Autoimmune Encephalomyelitis.Journal of visualized experiments : JoVE · 2023Article
- DNA Methylation Signatures of Multiple Sclerosis Occur Independently of Known Genetic Risk and Are Primarily Attributed to B Cells and Monocytes.International journal of molecular sciences · 2023Article
- Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis.Brain : a journal of neurology · 2023Article
- Integration of epigenetic and genetic profiles identifies multiple sclerosis disease-critical cell types and genes.Communications biology · 2023Article
- Differential impact of environmental factors on systemic and localized autoimmunity.Frontiers in immunology · 2023Review
- B cell targeted therapies in inflammatory autoimmune disease of the central nervous system.Frontiers in immunology · 2023Review
- Epigenetic regulation of B cells and its role in autoimmune pathogenesis.Cellular & molecular immunology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Epigenetic changes have been consistently detected in different cell types in multiple sclerosis (MS). However, their contribution to MS pathogenesis remains poorly understood partly because of sample heterogeneity and limited coverage of array-based methods. To fill this gap, we conducted a comprehensive analysis of genome-wide DNA methylation patterns in four peripheral immune cell populations isolated from 29 MS patients at clinical disease onset and 24 healthy controls. We show that B cells from new-onset untreated MS cases display more significant methylation changes than other disease-implicated immune cell types, consisting of a global DNA hypomethylation signature. Importantly, 4,933 MS-associated differentially methylated regions in B cells were identified, and this epigenetic signature underlies specific genetic programs involved in B cell differentiation and activation. Integration of the methylome to changes in gene expression and susceptibility-associated regions further indicates that hypomethylated regions are significantly associated with the up-regulation of cell activation transcriptional programs. Altogether, these findings implicate aberrant B cell function in MS etiology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.