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.
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.
Authors: Spyridon Chalkias; Xin Dang; Evelyn Bord; Marion C Stein; R Philip Kinkel; Jacob A Sloane; Maureen Donnelly; Carolina Ionete; Maria K Houtchens; Guy J Buckle; Stephanie Batson; Igor J Koralnik Journal: Ann Neurol Date: 2014-06-10 Impact factor: 10.422
Authors: Miriam Mattoscio; Richard Nicholas; Maria P Sormani; Omar Malik; Jean S Lee; Adam D Waldman; Francesco Dazzi; Paolo A Muraro Journal: Neurology Date: 2015-03-11 Impact factor: 9.910
Authors: Clemens Warnke; Gloria von Geldern; Philipp Markwerth; Thomas Dehmel; Robert Hoepner; Ralf Gold; Michael Pawlita; Tania Kümpfel; Mathias Mäurer; Martin Stangel; Florian Wegner; Reinhard Hohlfeld; Vera Straeten; Volker Limmroth; Thomas Weber; Derik Hermsen; Christoph Kleinschnitz; Hans-Peter Hartung; Mike P Wattjes; Anders Svenningson; Eugene Major; Tomas Olsson; Bernd C Kieseier; Ortwin Adams Journal: Ann Neurol Date: 2014-05-08 Impact factor: 10.422
Authors: Thomas F Benkert; Lena Dietz; Elena M Hartmann; Ellen Leich; Andreas Rosenwald; Edgar Serfling; Mathias Buttmann; Friederike Berberich-Siebelt Journal: PLoS One Date: 2012-12-20 Impact factor: 3.240