Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors

Arch Neurol. 2011 Nov;68(11):1428-31. doi: 10.1001/archneurol.2011.238.

Abstract

Background: Treatment with natalizumab, an antibody blocking the α4-integrin, is associated with increased numbers of circulating CD34+ cells in the peripheral blood of patients with multiple sclerosis.

Objective: To determine whether natalizumab mobilizes CD34+ cells from or inhibits homing to the bone marrow (BM).

Design: Fifty-two patients with relapsing-remitting multiple sclerosis treated with natalizumab were included. Flow cytometric analyses; polymerase chain reaction assays for JC (John Cunningham) virus DNA detection; and adhesion, migration, and apoptosis assays of immunomagnetically enriched peripheral blood and BM CD34+ cells were conducted. A comparison was made with CD34+ cells from granulocyte colony-stimulating factor-mobilized peripheral blood or steady-state BM of age- and sex-matched healthy donors.

Results: We found adhesion and migration of peripheral blood-derived CD34+ cells to be reduced. In BM aspirates from natalizumab-treated patients, the cellularity, the proportion, and the adhesive capacity of CD34+ cells were normal. The JC virus was undetectable.

Conclusions: Natalizumab mediates an increase in circulating CD34+ cells by interfering with homing to the BM. Thus, CD34+ cells appear unlikely to represent a source mobilizing JC virus out of the BM in patients treated with natalizumab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD34 / biosynthesis*
  • Antigens, CD34 / blood
  • Cell Migration Inhibition / drug effects
  • Cell Migration Inhibition / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Natalizumab
  • Receptors, Lymphocyte Homing / biosynthesis*
  • Receptors, Lymphocyte Homing / blood

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, CD34
  • Natalizumab
  • Receptors, Lymphocyte Homing