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Increased expression of miR-130b-5p in B cells and its modulation by glatiramer acetate in multiple sclerosis

      Objective/Background: B cells are implicated in the pathogenesis of multiple sclerosis (MS). Our objective was to identify microRNAs (miRNAs) expressed in B cells of MS patients applying Next Generation Sequencing (NGS), a high-throughput/sensitive tool to study disease pathogenesis, drug mechanisms, to discover new biomarkers and therapeutic targets.
      Design/Methods: B cells and monocytes were separated from healthy donors (HD), untreated and Glatiramer Acetate (GA)-treated MS patients. Expression of more than 2500 mature human miRNAs annotated in miRBase 20 was tested by NGS and validated by RT-qPCR. IRB approval was granted.
      Results: 370 and 443 miRNAs were detected in B cells and monocytes, respectively. In B cells and monocytes, respectively, expression of 21 and 12 miRNAs was significantly (p < 0.05) different in untreated MS patients compared to HD and expression of 19 and 13 miRNAs was different in GA-treated patients vs. untreated patients. The DIANA-mirPath software analysis identified that Adherent junction and Chemokine signaling (monocytes and B cells) and B cell receptor signaling (B cells) pathways are targets for these miRNAs. Expression of 3 miRNAs (miR-1295a, miR-450a-5p + 1, and miR-130b-5p) was increased in B cells of untreated MS patients and corrected/decreased by GA treatment. Expression levels of miR-130b-5p were increased by more than 100% in untreated MS patients compared to both HD and GA-treated patients based on both NGS and RT-qPCR results, p < 0.05.
      Conclusion: Expression of miR-130b-5p in B cells is increased in MS patients and is corrected by GA treatment. The physiological significance of this finding will be discussed.