Natalizumab effects on immune cell responses in multiple sclerosis
Article first published online: 21 APR 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 5, pages 748–754, May 2006
How to Cite
Niino, M., Bodner, C., Simard, M.-L., Alatab, S., Gano, D., Kim, H. J., Trigueiro, M., Racicot, D., Guérette, C., Antel, J. P., Fournier, A., Grand'Maison, F. and Bar-Or, A. (2006), Natalizumab effects on immune cell responses in multiple sclerosis. Ann Neurol., 59: 748–754. doi: 10.1002/ana.20859
- Issue published online: 21 APR 2006
- Article first published online: 21 APR 2006
- Manuscript Accepted: 11 MAR 2006
- Manuscript Revised: 3 MAR 2006
- Manuscript Received: 4 FEB 2006
Our objective was to study in vivo biological effects of natalizumab on immune cell phenotype and function in multiple sclerosis (MS) patients.
Blood was obtained before and after serial monthly natalizumab infusions to track functional expression of VLA-4 and migratory capacity of immune cells. The impact of infusion on activation thresholds of immune cells was evaluated.
Preinfusion VLA-4 expression differed across immune cell subsets. Natalizumab significantly, albeit partially, diminished VLA-4 expression on circulating immune cells. Cell subsets were differentially affected. Treatment significantly decreased migratory capacity of immune cells, correlating well with changes in VLA-4 expression. Effects of a single dose were not saturating and did not persist through the monthly dose interval. Infusion effect varied across patients but was remarkably stable in individual patients, over multiple infusions. Treatment significantly modulated proliferative responses of immune cells.
To our knowledge, we provide first proof of concept that natalizumab diminishes migratory capacity of immune cells. Our prospective study further shows that effects of therapy likely (1) differ for distinct immune cell subsets, (2) are not sustained over current dose interval, (3) have unique profiles in individual patients, and (4) include modulation of activation threshold of immune cells. Monitoring these parameters could be relevant to ongoing safety and efficacy considerations. Ann Neurol 2006;59:748–754