Activation of Type I Interferon Signal Pathway in Patients with Multiple Sclerosis by the Russian Analog of β-Interferon-1b (transcriptional profiling data)

Abstract

The introduction of Russian analogs of β-interferon (β-IFN) produced by recombinant strains of E. coli (β-IFN-1b) into medical practice in Russia for the pathogenetic treatment of multiple sclerosis (MS) requires, in accordance with contemporary standards, confirmation by transcriptome analysis that they activate the main signal pathways involved in the mechanism of action of β-IFN. In the present report we present such an analysis for Infibeta (produced by Generium). Whole-genome transcription profiling using an Illumina HT-12 microarray was performed to identify genes showing differential expression in peripheral blood mononuclear cells from MS patients in response to exposure to this agent. Comparison of the levels of gene expression in MS patients not previously treated with any kind of immunomodulatory therapy before and 10 h after the first dose of agent identified 490 genes whose expression showed statistically significant changes, of which 191 genes showed increases in expression (up-regulated genes) and 299 genes showed decreases in expression (down-regulated genes). These genes included genes from the inflammation system, the innate and adaptive immune systems, apoptosis, signal transmission, transcription, translation, and degradation. Analysis of the overall expression of sets (groups) of genes (gene set analysis) yielded data which may provide evidence that IFN type I signal pathway genes, as well as IFN-induced genes, are involved in patients’ responses to the agent. Thus, analysis by transcriptional profiling led to the conclusion that the mechanism of the immunomodulatory action of Infibeta is identical to that described for original β-IFN formulations.