An Inventory of Short Term and Long Term Changes in Gene Expression Under Interferon beta Treatment of Relapsing Remitting MS Patients

作者：Paap Brigitte K; Hundeshagen Alexander; Hecker Michael; Zettl Uwe K^*

来源：Current Pharmaceutical Design, 2012, 18(29): 4475-4484.

• Multiple sclerosis
• type I interferons
• expression pattern
• signalling pathway
• immunotherapy
• gene regulation
• systems biology

Multiple sclerosis (MS) is a chronic immune modulated disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal injury. Currently relapsing remitting type of MS patients are most commonly treated with immune-modulators like interferon beta (IFN beta) or glatiramer acetate (GA). However, while the majority of patients respond well to therapy others do not. Gene expression profiles in blood samples taken over the course of IFN beta treatment can document changes in the biology of the patients in response to the drug and disease activity. During the last decade quite a few of such studies profiling expression in response to IFN beta treatment had been done. Here, we combine the results of these studies to outline common differential expression patterns in peripheral blood mononuclear cells (PBMCs) over the course of time under IFN beta treatment. We set these profiles into the picture of current knowledge about IFN beta pathway, MS immunology and IFN beta mechanisms of action. IFN beta modulates hundreds of genes. In most of the studies the prominent ones like MX 1, OAS 1, and CXCL 10 had been found to be influenced by IFN beta drug treatment. We show examples of short term and long term induced expressional changes, up and down regulated genes (STAT1 and IL8), and explain how under drug treatment feedback loops of type I IFN (IFN alpha and IFN beta) regulated genes may be modulated and changes in expression patterns may result in cytological changes.

• 出版日期2012-10