[The activation of the type I interferon signaling pathway in multiple sclerosis patients treated with russian...

Implementation of the analogues of Β-interferon (Β-IFN), produced by recombinant strains of E. coli (Β-IFN-1b), for internal use in the Russian Federation for the treatment of multiple sclerosis (MS), implies a verification of their action at the transcriptome level in order to confirm the activation of the main signaling pathways involved in IFNb mechanism of action. In this work, the analysis is carried out for Infibeta (Generium, Russia). Using genome-wide transcriptional profiling with ILLUMINA HT-12 microarray, the differentially expressed genes in peripheral blood mononuclear cells of MS patients upon administration of Infibeta were studied. Comparison of gene expression levels in treatment-naive MS patients prior to first Β-IFN administration and 10 hours after it, identified 490 genes with significantly changed expression level, where 191 genes were up-regulated and 299 genes were down-regulated. Among the involved genes are those coding the components of the inflammatory system, innate and adaptive immunity, apoptosis, signal transduction, transcription, translation, degradation. Using gene set analysis, we confirmed the involvement of type I interferon signaling pathway genes and interferon-inducible genes in a patient's individual response to drug. Thus, the transcriptome profiling analysis allows concluding that the mechanism of action of Infibeta immunomodulatory drug is equal to that described for the original Β-IFN drugs.