title: Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis.
abstract: Autoimmune diseases such as multiple sclerosis are characterized by complex genetic traits and pathomechanisms that translate into clinical heterogeneity. This wide heterogeneity of multiple sclerosis as well as different biological responses to immunomodulatory drugs can be expected to contribute to differential treatment responses. Strategies that dissect the relationship between the treatment response and the biological characteristics in individual patients are valuable not only as a clinical tool, but also in leading to a better understanding of the disease. Here we address the in vitro and ex vivo RNA expression profile under one approved therapy of multiple sclerosis, interferon-beta (IFN-beta, Betaseron), by cDNA microarrays and demonstrate that non-responder and responder phenotypes to IFN-beta as assessed by longitudinal gadolinium-enhanced MRI scans and clinical disease activity differ in their ex vivo gene expression profile. These findings will help to better elucidate the mechanism of action of IFN-beta in relation to different disease patterns and eventually lead to optimized therapy.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stürzebecher
authors.forename: K P
authors.initials: KP
authors.lastname: Wandinger
authors.forename: A
authors.initials: A
authors.lastname: Rosenwald
authors.forename: M
authors.initials: M
authors.lastname: Sathyamoorthy
authors.forename: A
authors.initials: A
authors.lastname: Tzou
authors.forename: P
authors.initials: P
authors.lastname: Mattar
authors.forename: J A
authors.initials: JA
authors.lastname: Frank
authors.forename: L
authors.initials: L
authors.lastname: Staudt
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.forename: H F
authors.initials: HF
authors.lastname: McFarland
mesh_terms: D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta