Trial reportThe Journal of clinical investigation2012
Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.
Trial report in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Serum adenosine deaminase activity is increased in systemic lupus erythematosus patients and correlated with disease activity.Immunologic research · 2018Trial
- Human genetic influences on early B cell development.Journal of human immunity · 2025Review
- Review
- Anti-cytokine autoantibodies: mechanistic insights and disease associations.Nature reviews. Immunology · 2024Review
- Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD.JCI insight · 2023Article
- "Cutting the Mustard" with Induced Pluripotent Stem Cells: An Overview and Applications in Healthcare Paradigm.Stem cell reviews and reports · 2022Review
- Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.The Journal of clinical investigation · 2022Article
- Positive and negative selection shape the human naive B cell repertoire.The Journal of clinical investigation · 2022Article
- Antinuclear Antibodies With a Nucleolar Pattern Are Associated With a Significant Reduction in the Overall Survival of Patients With Leukemia: A Retrospective Cohort Study.Frontiers in oncology · 2021Article
- B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects.Frontiers in immunology · 2021Review
- Dosing and Re-Administration of Lentiviral Vector forMolecular therapy. Methods & clinical development · 2020Article
- Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies.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
- Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency.The Journal of allergy and clinical immunology · 2019Review
- Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation.Frontiers in immunology · 2019Review
- Mechanisms underlying B cell immune dysregulation and autoantibody production in MuSK myasthenia gravis.Annals of the New York Academy of Sciences · 2018Review
- A map of human circular RNAs in clinically relevant tissues.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Multiparametric Whole Blood Dissection: A one-shot comprehensive picture of the human hematopoietic system.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2017Article
- Mechanisms of central tolerance for B cells.Nature reviews. Immunology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Adenosine deaminase (ADA) gene defects are among the most common causes of SCID. Restoration of purine metabolism and immune functions can be achieved by enzyme replacement therapy, or more effectively by bone marrow transplant or HSC gene therapy (HSC-GT). However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. To assess whether ADA deficiency affects the establishment of B cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells of ADA-SCID patients before and after HSC-GT. We found that before HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients contained more autoreactive and ANA-expressing clones, indicative of defective central and peripheral B cell tolerance checkpoints. We further observed impaired B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells. Hence, ADA plays an essential role in controlling autoreactive B cell counterselection by regulating BCR and TLR functions.
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Registered trials
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.