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Forschungsdatenbank PMU-SQQUID

Molecular evidence of transient therapeutic effectiveness of natalizumab despite high-titre neutralizing antibodies.
Pilz, G; Harrer, A; Oppermann, K; Wipfler, P; Golaszewski, S; Afazel, S; Haschke-Becher, E; Trinka, E; Kraus, J;
Mult Scler. 2012; 18(4):506-509
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Golaszewski Stefan
Harrer Andrea
Haschke-Becher Elisabeth
Kraus Jörg
Oppermann Katrin
Pilz Georg
Trinka Eugen
Wipfler Peter

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.


Useful keywords (using NLM MeSH Indexing)

Adult

Antibodies, Monoclonal, Humanized/immunology

Antibodies, Monoclonal, Humanized/therapeutic use*

Antibodies, Neutralizing/immunology

Antibodies, Neutralizing/therapeutic use*

Female

Flow Cytometry

Humans

Integrin alpha4beta1/immunology

Leukocytes, Mononuclear/immunology

Leukocytes, Mononuclear/metabolism

Multiple Sclerosis, Relapsing-Remitting/drug therapy*

Multiple Sclerosis, Relapsing-Remitting/immunology*

Natalizumab

Vascular Cell Adhesion Molecule-1/blood


Find related publications in this database (Keywords)

alpha-4 integrin
multiple sclerosis
natalizumab
neutralizing antibodies