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IFN-beta-regulated genes show abnormal expression in therapy-naïve relapsing-remitting MS mononuclear cells: gene expression analysis employing all reported protein-protein interactions.

Research paper by Ken D KD Yamaguchi, Daniel L DL Ruderman, Ed E Croze, T Charis TC Wagner, Sharlene S Velichko, Anthony T AT Reder, Hugh H Salamon

Indexed on: 19 Feb '08Published on: 19 Feb '08Published in: Journal of Neuroimmunology



Abstract

The molecular mechanism by which interferon beta (IFN-beta) is effective in treating multiple sclerosis is not well understood. Mononuclear cells from therapy-naïve MS patients, IFN-beta-1b-treated MS patients, and healthy controls were analyzed to examine mRNA changes that characterize both the disease and its treatment. The scientific literature was comprehensively searched for all protein-protein interactions. In MS patients who had never been treated with IFN-beta, statistical analysis revealed coordinate changes in mRNA expression for proteins reported in the literature as "regulated by IFN-beta." As a positive control for this approach, samples from a separate MS patient cohort showed significant change of these same genes during in vivo treatment with IFN-beta-1b.The strength of effect observed for regulation by IFN-beta was greater than for IFN-alpha, IFN-gamma (Th1), or IL-4 (Th2). Of the sets we investigated, the most strongly affected by disease was the subset defined by regulation by both IFN-beta and IFN-alpha. Changes in cells from therapy-naïve MS patients thus anticipated the importance of IFN-beta in therapy. These findings are a significant step towards marrying MS disease etiology and IFN-beta mechanism of action at a molecular level.