title: Natalizumab therapy decreases surface expression of both VLA-heterodimer subunits on peripheral blood mononuclear cells.
abstract: 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.
authors: Christian-Doppler-Klinik, Department of Neurology, Paracelsus Medical University, Salzburg, Austria. a.harrer@salk.at
authors: Andrea
authors: A
authors: Harrer
authors: Peter
authors: P
authors: Wipfler
authors: Max
authors: M
authors: Einhaeupl
authors: Georg
authors: G
authors: Pilz
authors: Katrin
authors: K
authors: Oppermann
authors: Wolfgang
authors: W
authors: Hitzl
authors: Shahrzad
authors: S
authors: Afazel
authors: Elisabeth
authors: E
authors: Haschke-Becher
authors: Peter
authors: P
authors: Strasser
authors: Eugen
authors: E
authors: Trinka
authors: Joerg
authors: J
authors: Kraus
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D000069442:Natalizumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D039041:Integrin alpha4beta1; D000069442:Natalizumab