ArticleThe Journal of clinical investigation2001
Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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.
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Who cites it
53 citing papers in PubMed, 109 citations in OpenAlex.
- Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.The Journal of clinical investigation · 2012Trial
- Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.Blood · 2008Trial
- Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.Cancer immunology research · 2023Article
- Clinical applications of gene therapy for rare diseases: A review.International journal of experimental pathology · 2023Review
- Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China.World journal of pediatrics : WJP · 2023Article
- Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function.bioRxiv : the preprint server for biology · 2023Article
- Review
- Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis.Frontiers in immunology · 2022Article
- Enzymatic deamination of the epigenetic nucleoside N6-methyladenosine regulates gene expression.Nucleic acids research · 2021Article
- Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy.Scientific reports · 2021Article
- Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.Journal of clinical immunology · 2021Article
- Nucleotide Pool Imbalance and Antibody Gene Diversification.Vaccines · 2021Review
- The Use of Induced Pluripotent Stem Cells to Study the Effects of Adenosine Deaminase Deficiency on Human Neutrophil Development.Frontiers in immunology · 2021Article
- Comparison of elapegademase and pegademase in ADA-deficient patients and mice.Clinical and experimental immunology · 2020Article
- Therapeutic Perspectives of Molecules fromMolecules (Basel, Switzerland) · 2019Review
- The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.Pharmacological reviews · 2019Review
- Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV.Nature communications · 2019Article
- The critical role of dysregulation of antioxidant activity and carbohydrate metabolism in celiac disease.Gastroenterology and hepatology from bed to bench · 2019Article
- Early Enzyme Replacement Therapy Improves Hearing and Immune Defects in Adenosine Deaminase Deficient-Mice.Frontiers in immunology · 2019Article
- Early-onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms.Immunological reviews · 2019Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Adenosine deaminase (ADA) deficiency in humans results in a severe combined immunodeficiency (SCID). This immunodeficiency is associated with severe disturbances in purine metabolism that are thought to mediate lymphotoxicity. The recent generation of ADA-deficient (ADA(-/-)) mice has enabled the in vivo examination of mechanisms that may underlie the SCID resulting from ADA deficiency. We demonstrate severe depletion of T and B lymphocytes and defects in T and B cell development in ADA(-/-) mice. T cell apoptosis was abundant in thymi of ADA(-/-) mice, but no increase in apoptosis was detected in the spleen and lymph nodes of these animals, suggesting that the defect is specific to developing thymocytes. Studies of mature T cells recovered from spleens of ADA(-/-) mice revealed that ADA deficiency is accompanied by TCR activation defects of T cells in vivo. Furthermore, ex vivo experiments on ADA(-/-) T cells demonstrated that elevated adenosine is responsible for this abnormal TCR signaling. These findings suggest that the metabolic disturbances seen in ADA(-/-) mice affect various signaling pathways that regulate thymocyte survival and function. Experiments with thymocytes ex vivo confirmed that ADA deficiency reduces tyrosine phosphorylation of TCR-associated signaling molecules and blocks TCR-triggered calcium increases.
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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.