Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.

Area of Science:

• Neuroimmunology
• Genomics
• Molecular Biology

Background:

• Multiple sclerosis (MS), predominantly Relapsing-Remitting MS (RRMS), has unknown molecular drivers of progression.
• Whole-genome gene expression analysis is crucial for understanding RRMS pathogenesis.

Purpose of the Study:

• To investigate the molecular mechanisms underlying Relapsing-Remitting Multiple Sclerosis (RRMS) progression.
• To identify sex-specific differences in gene expression patterns during MS remission and relapse.

Main Methods:

• Whole-genome gene expression analysis using Affymetrix Human Gene 1.0 ST microarrays.
• Comparative analysis of peripheral blood leukocytes from 25 RRMS patients (remission/relapse) and 25 healthy controls.
• Coexpression network analysis to identify gene modules.

Main Results:

• 174 genes showed altered expression in both remission and relapse states in RRMS patients.
• A significant proportion of these genes exhibited a "mirror pattern" (upregulated in one state, downregulated in the other).
• Coexpression analysis revealed three female-specific and one male-specific gene modules.

Conclusions:

• Epstein-Barr virus (EBV) reactivation in B cells is implicated in MS relapses, particularly in females.
• Neutrophil priming in females may be an endogenous mechanism to control EBV reactivation via vitamin B12.
• Non-coding RNA plays a significant sex-specific role in MS pathogenesis.