Human Gene Set: HECKER_IFNB1_TARGETS


Standard name HECKER_IFNB1_TARGETS
Systematic name M3010
Brief description Genes transcriptionally modulated in the blood of multiple sclerosis patients in response to subcutaneous treatment with recombinant IFNB1 [GeneID=3456].
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 23636981   Authors: Hecker M,Hartmann C,Kandulski O,Paap BK,Koczan D,Thiesen HJ,Zettl UK
Exact source Table 1S
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Organism Homo sapiens
Contributed by Michael Hecker (Steinbeis Foundation)
Source platform Human_NCBI_Gene_ID
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NCI-60 cell lines (National Cancer Institute)
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Version history 4.0: First introduced

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