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.
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 MSpatients 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: A Bellizzi; C Nardis; E Anzivino; D M Rodìo; D Fioriti; M Mischitelli; F Chiarini; V Pietropaolo Journal: J Neurovirol Date: 2012-02 Impact factor: 2.643
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: Martin Duddy; Aiden Haghikia; Eleonora Cocco; Christian Eggers; Jelena Drulovic; Olga Carmona; Helene Zéphir; Ralf Gold Journal: J Neurol Date: 2011-03-25 Impact factor: 4.849
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