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

The molecular mechanism by which interferon beta (IFN-β) is effective in treating multiple sclerosis is not well understood. Mononuclear cells from therapy-naïve MS patients, IFN-β-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-β, statistical analysis revealed coordinate changes in mRNA expression for proteins reported in the literature as “regulated by IFN-β.” 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-β-1b.The strength of effect observed for regulation by IFN-β was greater than for IFN-α, IFN-γ (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-β and IFN-α. Changes in cells from therapy-naïve MS patients thus anticipated the importance of IFN-β in therapy. These findings are a significant step towards marrying MS disease etiology and IFN-β mechanism of action at a molecular level.