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

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.

• Authors: Clemens Warnke, Vsevolod Smolianov, Thomas Dehmel, Marcel Andrée, Hartmut Hengel, Fabian Zohren, Gabriele Arendt, Heinz Wiendl, Rainer Haas, Hans-Peter Hartung, Ortwin Adams, Bernd C Kieseier
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 17 Issue 2 Pg. 151-6 (Feb 2011) ISSN: 1477-0970 [Electronic] England
• PMID: 21078695 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, immunology, virology)
• Humans
• Immunologic Factors (adverse effects)
• JC Virus (genetics)
• Leukoencephalopathy, Progressive Multifocal (blood, chemically induced, virology)
• Male
• Multiple Sclerosis, Relapsing-Remitting (drug therapy)
• Natalizumab
• Risk Assessment
• Risk Factors
• Time Factors
• Young Adult