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Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis
Ivan Kiselev1, Ludmila Danilova2, Natalia Baulina1
1Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Ostrovityanova st. 1, Moscow 117997, Russian Federation.
Abstract:
Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological process. To identify MS-associated DNA methylation hallmarks, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same treatment-naive relapsing-remitting MS patients and healthy subjects, using Illumina 450 K methylation arrays. We revealed significant changes in DNA methylation for both cell populations in MS. In CD4+ cells of MS patients the majority of differentially methylated positions (DMPs) were shown to be hypomethylated, while in CD14+ cells - hypermethylated. Differential methylation of HLA-DRB1 gene in CD4+ and CD14+ cells was associated with carriage of DRB1*15 allele independently from the disease status. Besides, about 20% of identified DMPs were shared between two cell populations and had the same direction of methylation changes; they may be involved in basic epigenetic processes occuring in MS. These findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to MS; further studies are now required to validate these results and understand their functional significance.
Insights
Epigenetic changes in DNA methylation are linked to multiple sclerosis (MS). This study identified specific DNA methylation patterns in immune cells of MS patients, suggesting a role for epigenetics in MS development.
Area of Science:
- Neuroimmunology
- Epigenetics
- Central Nervous System Disorders
Background:
- Multiple sclerosis (MS) is a chronic autoimmune CNS disease influenced by genetic and environmental factors.
- Environmental triggers like infections and smoking may impact DNA methylation, an epigenetic mechanism implicated in MS pathogenesis.
- Understanding epigenetic alterations in immune cells is crucial for elucidating MS development.
Purpose of the Study:
- To identify DNA methylation hallmarks associated with multiple sclerosis (MS).
- To compare genome-wide DNA methylation profiles in immune cells from MS patients and healthy controls.
- To investigate the role of epigenetic modifications in the development of MS.
Main Methods:
- Genome-wide DNA methylation profiling was performed using Illumina 450K methylation arrays.
- Two immune cell populations, CD4+ T-lymphocytes and CD14+ monocytes, were analyzed from treatment-naive relapsing-remitting MS patients and healthy subjects.
- Differential methylation analysis was conducted to identify MS-associated differentially methylated positions (DMPs).
Main Results:
- Significant DNA methylation changes were observed in both CD4+ T-lymphocytes and CD14+ monocytes of MS patients.
- CD4+ cells showed predominantly hypomethylation, while CD14+ cells exhibited hypermethylation in MS.
- Differential methylation of the HLA-DRB1 gene was associated with the DRB1*15 allele, and approximately 20% of DMPs were shared between cell types.
Conclusions:
- Epigenetic mechanisms, specifically DNA methylation in immune cells, contribute to the pathogenesis of multiple sclerosis.
- Identified DNA methylation patterns may serve as biomarkers or targets for future MS research.
- Further studies are warranted to validate these findings and explore the functional significance of DNA methylation in MS.

