Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients.
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.
Lindberg
Raija L P
RL
Clinical Neuroimmunology Laboratory, Departments of Research and Neurology, University Hospital Basel, Switzerland. Raija.lindberg@unibas.ch
Achtnichts
Lutz
L
Hoffmann
Francine
F
Kuhle
Jens
J
Kappos
Ludwig
L
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007109:Immunity / Q000235:genetics; D039441:Integrin alpha4 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000069442:Natalizumab; D016032:Randomized Controlled Trials as Topic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D000069442:Natalizumab; D039441:Integrin alpha4