title: 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.affiliation: Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. bernd.kieseier@uni_duesseldorf.de
authors.forename: Clemens
authors.initials: C
authors.lastname: Warnke
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Smolianov
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.forename: Marcel
authors.initials: M
authors.lastname: Andrée
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Fabian
authors.initials: F
authors.lastname: Zohren
authors.forename: Gabriele
authors.initials: G
authors.lastname: Arendt
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34 / Q000032:analysis*; D002465:Cell Movement / Q000187:drug effects*; D003587:Cytomegalovirus / Q000235:genetics; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D005858:Germany; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007577:JC Virus / Q000235:genetics*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood / Q000139:chemically induced* / Q000821:virology; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D004279:DNA, Viral; D007155:Immunologic Factors; D000069442:Natalizumab