Molecular evidence of transient therapeutic effectiveness of natalizumab despite high-titre neutralizing antibodies.
Mult Scler
; 18(4): 506-9, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-21965415
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esclerosis Múltiple Recurrente-Remitente
/
Anticuerpos Neutralizantes
/
Anticuerpos Monoclonales Humanizados
Límite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Mult Scler
Asunto de la revista:
NEUROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Austria