학술논문

Molecular evidence of transient therapeutic effectiveness of natalizumab despite high-titre neutralizing antibodies.
Document Type
Article
Source
Multiple Sclerosis Journal. Apr2012, Vol. 18 Issue 4, p506-509. 4p. 1 Graph.
Subject
*BLOOD plasma
*IMMUNOGLOBULINS
*MONOCLONAL antibodies
*MULTIPLE sclerosis
*CELL communication
Language
ISSN
1352-4585
Abstract
Natalizumab is a humanized monoclonal antibody directed against the alpha-4 integrin subunit of very late activation antigen-4 (VLA-4). Natalizumab neutralizing antibodies (NAB) have been found to significantly reduce beneficial effects of natalizumab treatment in multiple sclerosis. We investigated interactions of NAB with natalizumab by serial measurements of alpha-4 integrin levels on peripheral blood mononuclear cells using flow cytometry. In addition, serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), the endothelial ligand of VLA-4, and serum NAB were serially determined. Natalizumab infusion led to a transient reduction in alpha-4 integrin levels on immune cells and serum sVCAM-1 levels along with serum negativity of NAB lasting for a few days post-infusion. Apparently, the high-dose effect of freshly infused natalizumab resulted in a transient neutralization of NAB possibly involving a transient therapeutic effectiveness. [ABSTRACT FROM PUBLISHER]