NDLI: Interferon-beta therapy in multiple sclerosis: the short-term and long-term effects on the patients’ individual gene expression in peripheral blood

Content Provider	Springer Nature Link
Author	Hecker, Michael Hartmann, Christiane Kandulski, Ole Paap, Brigitte Katrin Koczan, Dirk Thiesen, Hans Juergen Zettl, Uwe Klaus
Copyright Year	2013
Abstract	Therapy with interferon-beta (IFN-beta) is a mainstay in the management of relapsing–remitting multiple sclerosis (MS), with proven long-term effectiveness and safety. Much has been learned about the molecular mechanisms of action of IFN-beta in the past years. Previous studies described more than a hundred genes to be modulated in expression in blood cells in response to the therapy. However, for many of these genes, the precise temporal expression pattern and the therapeutic relevance are unclear. We used Affymetrix microarrays to investigate in more detail the gene expression changes in peripheral blood mononuclear cells from MS patients receiving subcutaneous IFN-beta-1a. The blood samples were obtained longitudinally at five different time points up to 2 years after the start of therapy, and the patients were clinically followed up for 5 years. We examined the functions of the genes that were upregulated or downregulated at the transcript level after short-term or long-term treatment. Moreover, we analyzed their mutual interactions and their regulation by transcription factors. Compared to pretreatment levels, 96 genes were identified as highly differentially expressed, many of them already after the first IFN-beta injection. The interactions between these genes form a large network with multiple feedback loops, indicating the complex crosstalk between innate and adaptive immune responses during therapy. We discuss the genes and biological processes that might be important to reduce disease activity by attenuating the proliferation of autoreactive immune cells and their migration into the central nervous system. In summary, we present novel insights that extend the current knowledge on the early and late pharmacodynamic effects of IFN-beta therapy and describe gene expression differences between the individual patients that reflect clinical heterogeneity.
Starting Page	737
Ending Page	756
Page Count	20
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	48
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2013-05-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Interferon-beta Multiple sclerosis Peripheral blood Gene expression Network analysis Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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