Trial reportBlood2008
Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.
Trial report in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00598481 (ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID), which is not on this map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
Who cites it
32 citing papers in PubMed, 75 citations in OpenAlex.
- Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.The Journal of clinical investigation · 2012Trial
- Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell.EMBO molecular medicine · 2011Trial
- Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer.Nature immunology · 2025Article
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- ADA/CD26 axis increases intra-tumor PD-1Oncoimmunology · 2024Article
- Plasma adenosine deaminase-1 and -2 activities are lower at birth in Papua New Guinea than in The Gambia but converge over the first weeks of life.Frontiers in immunology · 2024Article
- Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.Cancer immunology research · 2023Article
- Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function.bioRxiv : the preprint server for biology · 2023Article
- 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
- The Use of Induced Pluripotent Stem Cells to Study the Effects of Adenosine Deaminase Deficiency on Human Neutrophil Development.Frontiers in immunology · 2021Article
- Protein Arginine Methyltransferase 5 in T Lymphocyte Biology.Trends in immunology · 2020Review
- The emerging landscape of circular RNAs in immunity: breakthroughs and challenges.Biomarker research · 2020Review
- Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV.Nature communications · 2019Article
- Early Enzyme Replacement Therapy Improves Hearing and Immune Defects in Adenosine Deaminase Deficient-Mice.Frontiers in immunology · 2019Article
- Circular RNAs in immune responses and immune diseases.Theranostics · 2019Review
- A map of human circular RNAs in clinically relevant tissues.Journal of molecular medicine (Berlin, Germany) · 2017Article
- PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity.Scientific reports · 2016Article
- Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency.Frontiers in immunology · 2016Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in the adenosine deaminase (ADA) gene are responsible for a form of severe combined immunodeficiency (SCID) caused by the lymphotoxic accumulation of ADA substrates, adenosine and 2'-deoxy-adenosine. The molecular mechanisms underlying T-cell dysfunction in humans remain to be elucidated. Here, we show that CD4(+) T cells from ADA-SCID patients have severely compromised TCR/CD28-driven proliferation and cytokine production, both at the transcriptional and protein levels. Such an impairment is associated with an intrinsically reduced ZAP-70 phosphorylation, Ca(2+) flux, and ERK1/2 signaling and to defective transcriptional events linked to CREB and NF-kappaB. Moreover, exposure to 2'-deoxy-adenosine results in a stronger inhibition of T-cell activation, mediated by the aberrant A(2A) adenosine receptor signaling engagement and PKA hyperactivation, or in a direct apoptotic effect at higher doses. Conversely, in T cells isolated from patients after gene therapy with retrovirally transduced hematopoietic stem/progenitor cells, the biochemical events after TCR triggering occur properly, leading to restored effector functions and normal sensitivity to apoptosis. Overall, our findings provide a better understanding of the pathogenesis of the immune defects associated with an altered purine metabolism and confirm that ADA gene transfer is an efficacious treatment for ADA-SCID. The trials in this study are enrolled at www.ClinicalTrials.gov as #NCT00598481 and #NCT0059978.
Indexed as
Identifiers
What OpenQuestion holds
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.