Interferon-beta-1b-induced short- and long-term signatures of treatment activity in multiple sclerosis.

ABSTRACT: Interferon beta (IFN?) reduces disease burden in relapsing-remitting multiple sclerosis (MS) patients. In this study, IFN?-1b-treated MS patient gene expression profiles and biological knowledgebases were integrated to study IFN?'s pleiotropic mechanisms of action. Genes involved in immune regulation, mitochondrial fatty acid metabolism and antioxidant activity were discovered. Plausible mediators of neuronal preservation included NRF2, downregulation of OLA1, an antioxidant suppressor, and the antioxidant gene ND6, implicated in optic neuropathy and MS-like lesions. Network analysis highlighted IKBKE, which likely has a role in both viral response and energy metabolism. A comparative analysis of therapy-naive MS- and IFN?-associated gene expression suggests an IFN? insufficiency in MS. We observed more gene expression changes in long-term treatment than during acute dosing. These distinct short- and long-term effects were driven by different transcription factors. Multi-gene biomarker signatures of IFN? treatment effects were developed and subsequently confirmed in independent IFN?-1b-treated MS studies, but not in glatiramer acetate-treated patients.

SUBMITTER: Croze E 

PROVIDER: S-EPMC3793239 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature