[Interferon -beta therapy in multiple sclerosis].
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) white matter mediated by an autoimmune process, whose development is triggered by a complex interplay of multiple genetic and environmental factors. Interferon-beta (IFNbeta) substantially reduces clinical exacerbation and MRI disease activity in MS, possibly by inhibiting the antigen-presenting capacity, by reversing a Th1 shift of the immune response, and by suppressing the transmigration of autoreactive T cells into the CNS. However, it has become evident that a significant number of MS patients do not well respond to IFNbeta and experience adverse effects. Using a DNA microarray, we have recently identified a battery of IFN-responsive genes (IRG) in peripheral blood lymphocytes, which play a key role in biological effects of IFNbeta in MS. They include IRF-7, a positive feedback regulator of IFNbeta production, IFI30 and TAP1, a key component of the antigen-presentation machinery, and TNFAIP6, a secreted protein with antiinflammatory activities. Furthermore, IFNbeta promptly induces proinflammatory chemokines and cytokines responsible for adverse effects in MS. Hierarchical clustering analysis of T cell gene expression profile discriminates four molecularly distinct subgroups of MS, associated with differential disease activity and therapeutic response to IFNbeta. A panel of IRG are upregulated persistently in IFNbeta responders but not in nonresponders after treatment. These observations suggest that DNA microarray analysis is valuable for designing and optimizing personalized treatment of MS.
Satoh
Jun-ichi
J
Department of Bioinformatics and Neuroinformatics, Meiji Pharmaceutical University.
D015551:Autoimmunity; D002490:Central Nervous System / Q000276:immunology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D050835:Interferon Regulatory Factors; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D013601:T-Lymphocytes / Q000276:immunology
D050835:Interferon Regulatory Factors; D016899:Interferon-beta