Lithium induced amelioration of a rat model of multiple sclerosis through the suppression of glycogen synthase kinase (GSK)-3 signaling

Abstract

Background: We have previously shown that response gene to complement (RGC)-32 and FasL mRNA expression are significantly lower in the peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. Objectives: We have now investigated the combined roles of RGC-32, FasL, and CDC2 as possible biomarkers of relapse and predictors of response to glatiramer acetate (GA) treatment in relapsing-remitting MS patients. Material and Methods: Over the course of 2 years, a cohort of 15 GA-treated MS patients was clinically monitored using the Expanded Disability Status Scale, and blood samples were collected at 0, 3, 6, and 12 months. Target gene mRNA expression was measured in patients’ isolated PBMCs by real-time quantitative PCR. Results: During relapses MS patients had a decreased expression of RGC-32 (P b 0.0001) and FasL (P b 0.0005) mRNA but no change in CDC2 when compared to stable MS patients. As compared to nonresponders, responders to GA treatment had significantly higher mRNA levels of RGC-32 (P b 0.0001) and FasL (P b 0.003) but no change in CDC2. Receiver operating characteristic analysis was used to assess the predictive power of each putative biomarker. The predictive values of relapse were 90% for RGC-32, and 84% for FasL; the predictive values of responsiveness to GA treatment were 85% for RGC-32 and 85% for FasL. Conclusion: Our data suggest that RGC-32 and FasL could serve as potential markers for the prediction of MS relapses and the evaluation of patients’ response to GA therapy.