IFN-β-regulated genes show abnormal expression in therapy-naive relapsing-remitting MS mononuclear cells:: Gene expression analysis employing all reported protein-protein interactions

The molecular mechanism by which interferon beta (IFN-beta) is effective in treating multiple sclerosis is not well understood. Mononuclear cells from therapy-naive 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-naive 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. (C) 2007 Elsevier B.V. All rights reserved.