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

Brigitte      K. Paap; Alexander      Hundeshagen; Michael      Hecker; Uwe      K. Zettl

doi:10.2174/138161212802502215

Abstract

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 β (IFN β) 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 β 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 β 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 β treatment. We set these profiles into the picture of current knowledge about IFN β pathway, MS immunology and IFN β mechanisms of action. IFN β 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 β 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 α and IFN β) regulated genes may be modulated and changes in expression patterns may result in cytological changes.

Keywords: Multiple sclerosis, type I interferons, expression pattern, signalling pathway, immunotherapy, gene regulation, systems biology, central nervous system (CNS), peripheral blood mononuclear cells (PBMCs), IFN β.