B-cell reconstitution after lentiviral vector-mediated gene therapy in patients with Wiskott-Aldrich syndrome

The Journal of Allergy and Clinical Immunology
Maria Carmina CastielloMarita Bosticardo

Abstract

Wiskott-Aldrich syndrome (WAS) is a severe X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and susceptibility to autoimmunity and lymphomas. Hematopoietic stem cell transplantation is the treatment of choice; however, administration of WAS gene-corrected autologous hematopoietic stem cells has been demonstrated as a feasible alternative therapeutic approach. Because B-cell homeostasis is perturbed in patients with WAS and restoration of immune competence is one of the main therapeutic goals, we have evaluated reconstitution of the B-cell compartment in 4 patients who received autologous hematopoietic stem cells transduced with lentiviral vector after a reduced-intensity conditioning regimen combined with anti-CD20 administration. We evaluated B-cell counts, B-cell subset distribution, B cell-activating factor and immunoglobulin levels, and autoantibody production before and after gene therapy (GT). WAS gene transfer in B cells was assessed by measuring vector copy numbers and expression of Wiskott-Aldrich syndrome protein. After lentiviral vector-mediated GT, the number of transduced B cells progressively increased in the peripheral blood of all patients. Lentiviral vector-transdu...Continue Reading

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Sep 13, 2015·Current Opinion in Pharmacology·Benjamin C HoughtonAdrian J Thrasher
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Aug 14, 2021·The Journal of Allergy and Clinical Immunology·Minghui HeLisa S Westerberg

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Methods Mentioned

BETA
flow cytometry
fluorescence-activated cell sorting

Clinical Trials Mentioned

NCT01515462

Software Mentioned

R package
FlowJo

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