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Updated: Aug 19, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple
Jun-ichi Satoh1, Megumi Nakanishi, Fumiko Koike
1Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Abstract:
To clarify the molecular mechanisms underlying multiple sclerosis (MS)-promoting autoimmune process, we have investigated a comprehensive gene expression profile of T cell and non-T cell fractions of peripheral blood mononuclear cells (PBMC) isolated from 72 MS patients and 22 age- and sex-matched healthy control (CN) subjects by using a cDNA microarray. Among 1258 genes examined, 173 genes in T cells and 50 genes in non-T cells were expressed differentially between MS and CN groups. Downregulated genes greatly outnumbered upregulated genes in MS. More than 80% of the top 30 most significant genes were categorized into apoptosis signaling-related genes of both proapoptotic and antiapoptotic classes. They included upregulation in MS of orphan nuclear receptor Nurr1 (NR4A2), receptor-interacting serine/threonine kinase 2 (RIPK2), and silencer of death domains (SODD), and downregulation in MS of TNF-related apoptosis-inducing ligand (TRAIL), B-cell CLL/lymphoma 2 (BCL2), and death-associated protein 6 (DAXX). Furthermore, a set of the genes involved in DNA repair, replication, and chromatin remodeling was downregulated in MS. These results suggest that MS lymphocytes show a complex pattern of gene regulation that represents a counterbalance between promoting and preventing apoptosis and DNA damage of lymphocytes.
Insights
Multiple sclerosis (MS) involves complex gene regulation in lymphocytes, with many genes related to apoptosis and DNA repair showing altered expression. This suggests a delicate balance between promoting and preventing cell death and damage in MS patients.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Multiple sclerosis (MS) is an autoimmune disease with complex underlying molecular mechanisms.
- Understanding gene expression in immune cells is crucial for elucidating MS pathogenesis.
Purpose of the Study:
- To investigate the comprehensive gene expression profile of T cells and non-T cells in MS patients.
- To identify differentially expressed genes and their roles in MS-related autoimmune processes.
Main Methods:
- Gene expression profiling using cDNA microarray.
- Analysis of peripheral blood mononuclear cells (PBMCs) from 72 MS patients and 22 healthy controls.
- Differential gene expression analysis between MS and control groups.
Main Results:
- 173 genes in T cells and 50 genes in non-T cells showed differential expression in MS patients.
- Downregulated genes were more prevalent than upregulated genes in MS.
- Apoptosis signaling genes (pro- and antiapoptotic) and DNA repair/replication genes were significantly altered in MS.
Conclusions:
- MS lymphocytes exhibit a complex gene regulation pattern.
- This pattern suggests a counterbalance between pathways promoting and preventing lymphocyte apoptosis and DNA damage.
- These findings offer insights into the molecular mechanisms of MS autoimmunity.
