Gene expression analysis of interferon-β treatment in multiple sclerosis

• Published in: Multiple sclerosis Vol. 14; no. 5; pp. 615 - 621
• Main Authors: Sellebjerg, F, Datta, P, Larsen, J, Rieneck, K, Alsing, I, Oturai, A, Svejgaard, A, Soelberg Sørensen, P, Ryder, LP
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2008; Arnold
• Subjects: Adult; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disability Evaluation; Down-Regulation - drug effects; Down-Regulation - immunology; Female; Gene Expression - drug effects; Gene Expression - immunology; Gene Expression Profiling; Humans; Immunologic Factors - therapeutic use; Interferon-beta - therapeutic use; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - physiology; Male; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - genetics; Neurology; Oligonucleotide Array Sequence Analysis; Up-Regulation - drug effects; Up-Regulation - immunology; microarray; gene expression profiling; interferon-β; multiple sclerosis; Nervous system diseases; Multiple sclerosis; Treatment; Central nervous system disease; Interferon; Degenerative disease; Gene expression; Inflammatory disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458507085976

Treatment with interferon-β (IFN-β) induces the expression of hundreds of genes in blood mononuclear cells, and the expression of several genes has been proposed as a marker of the effect of treatment with IFN-β. However, to date no molecules have been identified that are stably induced by treatment with IFN-β. We use DNA microarrays to study gene expression in 10 multiple sclerosis (MS) patients who began de novo treatment with IFN-β. After the first injection of IFN-β, the expression of 74 out of 3428 genes changed at least two-fold and statistically significantly (after Bonferroni correction). In contrast, we observed no persisting effects of IFN-β on gene expression. Among the most strongly induced genes was MXA, which has been used in previous biomarker studies in MS. In addition, the study identified the induction of LGALS9 and TCIR1G, involved in negative regulation of T helper type I immunity and T-cell activation, as novel effects of IFN-β therapy in MS.