title: Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors.
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).
  
  
  METHODS
  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.
authors.affiliation: Department of Hematology, Oncology, and Clinical Immunology, University of Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Christian.Saure@med.uni-duesseldorf.de
authors.forename: Christian
authors.initials: C
authors.lastname: Saure
authors.forename: Clemens
authors.initials: C
authors.lastname: Warnke
authors.forename: Fabian
authors.initials: F
authors.lastname: Zohren
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.forename: Ingmar
authors.initials: I
authors.lastname: Bruns
authors.forename: Ron P
authors.initials: RP
authors.lastname: Cadeddu
authors.forename: Christian
authors.initials: C
authors.lastname: Weigelt
authors.forename: Ute
authors.initials: U
authors.lastname: Fischer
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
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
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000096:biosynthesis* / Q000097:blood; D002464:Cell Migration Inhibition / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy; D000069442:Natalizumab; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D000069442:Natalizumab; D016201:Receptors, Lymphocyte Homing