PMU-Autor/inn/en
Golaszewski StefanAbstract
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
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alpha-4 integrin