PMU-Autor/inn/en
Harrer AndreaAbstract
Natalizumab interferes with immune cell migration into the central nervous system via blocking the alpha-4 subunit of very-late activation antigen-4 (VLA-4). Occurrence of rare but serious progressive multifocal leukoencephalopathy during prolonged natalizumab therapy of multiple sclerosis (MS) calls for a more detailed understanding of potential coeffects. We longitudinally studied alpha-4 and beta-1 surface levels on blood cells from 18 MS patients by flow cytometry. Expectedly, detectability of natalizumab-blocked alpha-4 was diminished on all investigated cell subsets. In addition, we report a concurrent and significant decrease of beta-1 surface levels on T-cells, B-cells, natural killer cells, and natural killer T cells, but not on monocytes. Uncovering secondary effects of natalizumab is mandatory to increase safety in MS therapy.
Useful keywords (using NLM MeSH Indexing)
Adult
Antibodies, Monoclonal/therapeutic use*
Antibodies, Monoclonal, Humanized
Antigens, CD/genetics
Antigens, CD/metabolism
Female
Flow Cytometry/methods
Gene Expression Regulation/drug effects
Gene Expression Regulation/physiology*
Humans
Integrin alpha4beta1/genetics
Integrin alpha4beta1/metabolism*
Leukocytes, Mononuclear/classification
Leukocytes, Mononuclear/drug effects*
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting/drug therapy*
Multiple Sclerosis, Relapsing-Remitting/pathology*
Natalizumab
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Natalizumab