Background: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by immune-mediated demyelination and axonal injury. Myelin-reactive IFN-γ-producing Th1 cells has been shown to play an important role in the development of MS. MicroRNAs (miRNAs) are a new class of small non-coding RNA molecules about 22 nucleotides long which regulate gene expression post-transcriptionally by binding to 3' UTR of their mRNA targets, and resulting in degradation or transcriptional repression of the targeted mRNA. Accumulating evidence supports that miRNA dysregulation is linked to the pathogenesis of autoimmune diseases that include MS. miR-29b expression has been shown to be upregulated in memory CD4+T cells from relapsing-remitting MS (RR-MS) patients, which may reflect chronic Th1 inflammation. Interferon beta (IFN-β) benefits patients with MS and reduces symptoms of the RR-MS. MxA is induced by type I interferon and predicts IFN-β response in MS patients. The aim of this study was to evaluate miR-29b variants and MxA expression and serum IFN-γ level in responders and non-responders to IFN-β treatment.
Methods: A total of 70 IFN-β treated RR-MS patients including 35 responders and 35 non-responders were enrolled. We analyzed the expression level of miR-29b variants and MxA using the peripheral blood of MS patients treated with IFN-β for more than one year. Real-time RT-PCR was performed to analyze miR-29b variants and MxA expression one year after initiation of IFN-β therapy. Serum cytokine level was measured by ELISA.
Results: The results indicated that the expression level of miR-29b-3p changed related to IFN-β response. Moreover, miR-29b-5p was downregulated under IFN-β treatment in responders versus non-responders. MxA level was significantly decreased in the responders. There was no change in IFN-γ level following treatment with IFN-β in the MS patients.
Conclusions: Our results might provide fundamentals for the development of new markers of the biological effects of IFN-β therapy.
Keywords: Interferon-beta; Multiple sclerosis; MxA; miR-29b-3p; miR-29b-5p.
Copyright © 2019. Published by Elsevier B.V.