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Gene expression analysis of interferon-β treatment in multiple sclerosis

Department of Neurology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, sellebjerg{at}dadlnet.dk

P Datta

Department of Neurology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Neurology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

J Larsen

Tissue Typing Laboratory, Department of Clinical Immunology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

K Rieneck

Institute of Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

I Alsing

Tissue Typing Laboratory, Department of Clinical Immunology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

A Oturai

Department of Neurology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

A Svejgaard

Tissue Typing Laboratory, Department of Clinical Immunology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

P Soelberg Sørensen

Department of Neurology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

LP Ryder

Tissue Typing Laboratory, Department of Clinical Immunology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

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.

Key Words: gene expression profiling • interferon-β • microarray • multiple sclerosis

This version was published on June 1, 2008

Multiple Sclerosis, Vol. 14, No. 5, 615-621 (2008)
DOI: 10.1177/1352458507085976


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