Expression profiling identifies responder and non‐responder phenotypes to interferon‐β in multiple sclerosis

• Published in: Brain (London, England : 1878) England : 1878), 2003-06, Vol.126 (6), p.1419-1429
• Main Authors: Stürzebecher, S., Wandinger, K. P., Rosenwald, A., Sathyamoorthy, M., Tzou, A., Mattar, P., Frank, J. A., Staudt, L., Martin, R., McFarland, H. F.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; cDNA microarrays; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; expression profile; Follow-Up Studies; Gd = gadolinium; Gene Expression Profiling - methods; Gene Expression Regulation; Humans; IFN = interferon; IL‐8 = interleukin‐8; INR = initial non‐responder; Interferon beta-1b; Interferon-beta - therapeutic use; interferon‐β; Magnetic Resonance Imaging; Medical sciences; multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - pathology; Multiple Sclerosis - therapy; NAb = neutralizing antibodies; NAbNR = non‐responder due to high titres of neutralizing antibodies; Neurology; Oligonucleotide Array Sequence Analysis - methods; PBMC = peripheral blood mononuclear cells; Phenotype; Polymerase Chain Reaction - methods; Prognosis; Recombinant Proteins - therapeutic use; Recurrence; RNA, Messenger - genetics; RR = relapsing–remitting; Treatment Failure; Treatment Outcome
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awg147

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‐β (IFN‐β, Betaseron), by cDNA microarrays and demonstrate that non‐responder and responder phenotypes to IFN‐β 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‐β in relation to different disease patterns and eventually lead to optimized therapy.