Hematopoietic mobilization: Potential biomarker of response to natalizumab in multiple sclerosis

Neurology
Miriam MattoscioPaolo A Muraro

Abstract

To ascertain the mobilization from the bone marrow and the functional relevance of the increased number of circulating hematopoietic stem and progenitor cells (HSPC) induced by the anti-α-4 integrin antibody natalizumab in patients with multiple sclerosis (MS). We evaluated CD45(low)CD34+ HSPC frequency by flow cytometry in blood from 45 natalizumab-treated patients (12 of whom were prospectively followed during the first year of treatment as part of a pilot cohort and 16 prospectively followed for validation), 10 untreated patients with MS, and 24 healthy donors. In the natalizumab-treated group, we also assessed sorted HSPC cell cycle status, T- and B-lymphocyte subpopulation frequencies (n = 29), and HSPC differentiation potential (n = 10). Natalizumab-induced circulating HSPC were predominantly quiescent, suggesting recent mobilization from the bone marrow, and were capable of differentiating ex vivo. Circulating HSPC numbers were significantly increased during natalizumab, but heterogeneously, allowing the stratification of mobilizer and nonmobilizer subgroups. Nonmobilizer status was associated with persistence of disease activity during treatment. The frequency of B cells and CD103+CD8+ regulatory T cells persistently in...Continue Reading

Citations

Jan 19, 2016·Frontiers in Immunology·Rui LiUNKNOWN MSSRF Canadian B cells in MS Team
Aug 8, 2015·Nature Reviews. Immunology·Calliope A DendrouManuel A Friese
Jul 28, 2016·Multiple Sclerosis and Related Disorders·Sara La GioiaSabrina Buoro
Apr 14, 2016·Journal of Neurology, Neurosurgery, and Psychiatry·C WangM H Barnett
Aug 2, 2016·Expert Review of Neurotherapeutics·Alba SimatsJoan Montaner
Sep 24, 2016·Journal of Crohn's & Colitis·Carolijn SmidsEllen G van Lochem
Oct 11, 2015·Multiple Sclerosis : Clinical and Laboratory Research·E SignorielloG Lus
Nov 10, 2015·Multiple Sclerosis Journal - Experimental, Translational and Clinical·Erin E LongbrakeAnne H Cross
Apr 15, 2016·Current Opinion in Neurology·Manuel ComabellaXavier Montalban
Aug 2, 2017·Science Immunology·Galina GabrielyHoward L Weiner
Apr 11, 2019·Therapeutic Advances in Neurological Disorders·Luisa KlotzHeinz Wiendl
Oct 20, 2020·Frontiers in Immunology·Kathy KhoyBrigitte Le Mauff
Nov 24, 2020·Journal of Neuroinflammation·Michelle NaughtonDenise C Fitzgerald

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