Natalizumab therapy decreases surface expression of both VLA-heterodimer subunits on peripheral blood mononuclear cells

J Neuroimmunol. 2011 May;234(1-2):148-54. doi: 10.1016/j.jneuroim.2011.03.001. Epub 2011 Mar 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Integrin alpha4beta1
  • Natalizumab