ArticleThe Journal of clinical investigation2015
Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study.The Lancet. Haematology · 2019Trial
- Positive and negative selection shape the human naive B cell repertoire.The Journal of clinical investigation · 2022Article
- Activation induced cytidine deaminase: An old friend with new faces.Frontiers in immunology · 2022Review
- Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome.Nature medicine · 2022Article
- RHO GTPases: from new partners to complex immune syndromes.Nature reviews. Immunology · 2021Review
- Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias.Journal of clinical medicine · 2021Review
- Autoimmunity in Wiskott-Aldrich Syndrome: Updated Perspectives.The application of clinical genetics · 2021Review
- Review
- Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells.The Journal of allergy and clinical immunology · 2020Article
- Understanding and measuring human B-cell tolerance and its breakdown in autoimmune disease.Immunological reviews · 2019Review
- Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production.Brain : a journal of neurology · 2019Article
- AIRE expression controls the peripheral selection of autoreactive B cells.Science immunology · 2019Observational
- Circular RNAs in immune responses and immune diseases.Theranostics · 2019Review
- Autonomous role of Wiskott-Aldrich syndrome platelet deficiency in inducing autoimmunity and inflammation.The Journal of allergy and clinical immunology · 2018Article
- Re-educating immunity in respiratory allergies: the potential for hematopoietic stem cell-mediated gene therapy.Journal of molecular medicine (Berlin, Germany) · 2018Review
- Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome.Journal of clinical immunology · 2018Review
- Hereditary thrombocytopenias: a growing list of disorders.Hematology. American Society of Hematology. Education Program · 2017Review
- A map of human circular RNAs in clinically relevant tissues.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Wiskott-Aldrich syndrome protein: Emerging mechanisms in immunity.European journal of immunology · 2017Review
- Quantitative Imaging Approaches to Study the CAR Immunological Synapse.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and high susceptibility to developing tumors and autoimmunity. Recent evidence suggests that B cells may be key players in the pathogenesis of autoimmunity in WAS. Here, we assessed whether WAS protein deficiency (WASp deficiency) affects the establishment of B cell tolerance by testing the reactivity of recombinant antibodies isolated from single B cells from 4 WAS patients before and after gene therapy (GT). We found that pre-GT WASp-deficient B cells were hyperreactive to B cell receptor stimulation (BCR stimulation). This hyperreactivity correlated with decreased frequency of autoreactive new emigrant/transitional B cells exiting the BM, indicating that the BCR signaling threshold plays a major role in the regulation of central B cell tolerance. In contrast, mature naive B cells from WAS patients were enriched in self-reactive clones, revealing that peripheral B cell tolerance checkpoint dysfunction is associated with impaired suppressive function of WAS regulatory T cells. The introduction of functional WASp by GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. We conclude that WASp plays an important role in the establishment and maintenance of B cell tolerance in humans and that restoration of WASp by GT is able to restore B cell tolerance in WAS patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.