Abstract
Natalizumab, the most recently approved treatment for relapsing multiple sclerosis (MS) exerts its action through binding to alpha4 integrins. We studied longitudinally gene expression profiles in peripheral blood of MS patients, treated with natalizumab for more than 2 years. The majority of altered genes relates to immune response, signal transduction, adhesion and metabolism. Not only gene expression relevant for T lymphocytes was altered, but also genes regulating B-lymphocyte, neutrophil and erythrocyte functions. Understanding these different gene effects and their interrelationships will provide more insights into additional mechanisms of action of natalizumab and possibly allow better prediction of adverse events.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Blood Cells / drug effects*
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Blood Cells / metabolism
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Cell Adhesion / drug effects
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Cell Adhesion / genetics
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Cell Movement / drug effects
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Cell Movement / genetics
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Cytokines / blood
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Energy Metabolism / drug effects
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Energy Metabolism / genetics
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Female
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Follow-Up Studies
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Gene Expression Regulation / drug effects*
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Humans
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Immunity / genetics
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Integrin alpha4 / immunology
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Male
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Middle Aged
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Multiple Sclerosis / blood*
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / genetics
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Multiple Sclerosis / pathology
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Natalizumab
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Randomized Controlled Trials as Topic
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Transcription, Genetic / drug effects*
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Cytokines
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Natalizumab
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Integrin alpha4