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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Antigens, T-Independent, Autoantibodies, B-Lymphocytes, Bone Marrow Transplantation, Disease Models, Animal, Gene Expression, Genetic Therapy, Genetic Vectors, Humans, Lentivirus, Mice, Mice, Inbred C57BL, Mice, Knockout, Recombinant Proteins, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein.
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Does lentiviral-mediated gene therapy lead to improvement of B-cell functionality in a murine model of Wiskott-Aldrich syndrome? Context: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency characterized by thrombocytopenia, eczema, infections, autoimmunity, and lymphomas. Transplantation of hematopoietic stem cells from HLA-identical donors is curative, but it is not available to all patients. We have developed a gene therapy (GT) approach for WAS by using a lentiviral vector encoding for human WAS promoter/cDNA (w1.6W) and demonstrated its preclinical efficacy and safety. To evaluate B-cell reconstitution and correction of B-cell phenotype in GT-treated mice. We transplanted Was(-/-) mice sublethally irradiated (700 rads) with lineage marker-depleted bone marrow wild-type cells, Was(-/-) cells untransduced or transduced with the w1.6W lentiviral vector and analyzed B-cell reconstitution in bone marrow, spleen, and peritoneum. Here we show that WAS protein(+) B cells were present in central and peripheral B-cell compartments from GT-treated mice and displayed the strongest selective advantage in the splenic marginal zone and peritoneal B1 cell subsets. After GT, splenic architecture was improved and B-cell functions were restored, as demonstrated by the improved antibody response to pneumococcal antigens and the reduction of serum IgG autoantibodies.
assistant
WAS GT leads to improvement of B-cell functions, even in the presence of a mixed chimerism, further validating the clinical application of the w1.6W lentiviral vector. Final Decision: yes