Trial reportBlood2012
Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID.
Trial report in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 104 citations in OpenAlex.
- Serum adenosine deaminase activity is increased in systemic lupus erythematosus patients and correlated with disease activity.Immunologic research · 2018Trial
- Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.British journal of cancer · 2016Trial
- Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.Science (New York, N.Y.) · 2013Trial
- Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.The Journal of clinical investigation · 2012Trial
- Dual-mechanism anti-CD73 antibodies CR201 and CR202 targeting distinct domains for cancer immunotherapy.Frontiers in immunology · 2026Article
- The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain.Purinergic signalling · 2025Review
- Immunosuppressive mechanisms and therapeutic targeting of regulatory T cells in ovarian cancer.Frontiers in immunology · 2025Review
- T Cell Subsets and Immune Homeostasis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- CD73, a significant protein in liver diseases.Frontiers in medicine · 2023Review
- Mitochondrial-regulated Tregs: potential therapeutic targets for autoimmune diseases of the central nervous system.Frontiers in immunology · 2023Review
- Regulatory T cells in inflammation and resolution of acute lung injury.The clinical respiratory journal · 2022Review
- Treg tissue stability depends on lymphotoxin beta-receptor- and adenosine-receptor-driven lymphatic endothelial cell responses.Cell reports · 2022Article
- The immunomodulatory function of adenosine in sepsis.Frontiers in immunology · 2022Review
- The Use of Induced Pluripotent Stem Cells to Study the Effects of Adenosine Deaminase Deficiency on Human Neutrophil Development.Frontiers in immunology · 2021Article
- Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease.Frontiers in immunology · 2021Review
- The yin and yang functions of extracellular ATP and adenosine in tumor immunity.Cancer cell international · 2020Review
- Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency.The Journal of allergy and clinical immunology · 2019Review
- Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Adenosine Generated by Regulatory T Cells Induces CD8BioMed research international · 2019Article
- CD4Frontiers in pediatrics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)-mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA-treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA(-/-) Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA-treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA-treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID.
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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.