1. Deciphering the shift from benign to active relapsing-remitting multiple sclerosis: Insights into T regulatory cell dysfunction and apoptosis regulation
- Author
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Anat Achiron, Rina Falb, Shay Menascu, David Magalashvili, Mathilda Mandel, Polina Sonis, and Michael Gurevich
- Subjects
Gene expression ,Multiple sclerosis ,T-cell regulation ,Apoptosis ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Relapsing-remitting multiple sclerosis (RRMS), a common demyelinating disease among young adults, follows a benign course in 10–15% of cases, where patients experience minimal neurological disability for a decade following disease onset. However, there is potential for these benign cases to transition into a clinically active, relapsing state. Objective: To elucidate the biological mechanisms underlying the transition from benign to active RRMS using gene expression analysis. Methods: We employed complementary-DNA microarrays to examine peripheral-blood gene expression patterns in patients with benign MS, defined as having a disease duration exceeding 10 years and an Expanded Disability Status Scale (EDSS) score of ≤3.0. We compared the gene expression pattern between patients who switched to active disease (Switching BMS) with those who maintained a benign state (Permanent-BMS) during an additional 5-year follow-up. Results: We identified two primary mechanisms linked to the transition from benign MS to clinically active disease. The first involves the suppression of regulatory T cell activity, and the second pertains to the dysfunction of nuclear receptor 4 A family-dependent apoptosis. These mechanisms collectively contribute to an augmented autoimmune response and increased disease activity. Conclusions: The intricate gene regulatory networks that operate in switching-BMS are related to suppression of immune tolerance and aberrant apoptosis. These findings may lead to new therapeutic targets to prevent the escalation to active disease.
- Published
- 2024
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