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CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus

Mult Scler. 2011 Feb;17(2):151-6. doi: 10.1177/1352458510385834. Epub 2010 Nov 15.

Abstract

Background: Progressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment in patients with multiple sclerosis (MS). It has been hypothesized that natalizumab mobilizes JC virus (JCV)-infected haematopoietic progenitor cells mediating viraemia and subsequently this disease.

Objective: The objective of this study was to investigate peripheral haematopoietic progenitor cells for evidence of JCV DNA in MS patients treated with natalizumab.

Methods: We assessed JCV and cytomegalovirus (CMV) DNA in magnetically separated CD34+ haematopoietic progenitor cells, peripheral blood mononuclear cells and plasma of 67 natalizumab-treated patients with MS and six PML patients.

Results: Viral DNA was not detectable in CD34+ haematopoietic progenitor or peripheral blood mononuclear cells from any sample. Two plasma samples from patients with MS while undergoing natalizumab treatment were JCV-positive. In one case clinically manifest PML developed 8 months thereafter.

Conclusions: Our findings do not support the hypothesis that natalizumab mobilizes JC virus-infected CD34+ cells from the bone marrow mediating JC viraemia. Notably, JC viraemia was detected in one patient with MS prior to developing clinical PML. This warrants further study.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD34 / analysis*
  • Cell Movement / drug effects*
  • Cytomegalovirus / genetics
  • DNA, Viral / metabolism
  • Female
  • Germany
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / virology
  • Humans
  • Immunologic Factors / adverse effects*
  • JC Virus / genetics*
  • Leukoencephalopathy, Progressive Multifocal / blood
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / virology
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD34
  • DNA, Viral
  • Immunologic Factors
  • Natalizumab