ArticleNature medicine2014
Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05040256 (Neurologic and Immunologic Characteristics of CTLA-4 and LRBA Hereditary Deficiency), which is not on this map. Cited by 454 papers, 4 of them syntheses that pooled it.
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.
Neurologic and Immunologic Characteristics of CTLA-4 and LRBA Hereditary Deficiency
Who cites it
454 citing papers in PubMed, 4 syntheses or guidelines pooled it, 808 citations in OpenAlex.
- Comprehensive evaluation of clinical phenotypes and pathogenic features in late-onset monogenic inflammatory bowel disease: a comparative study with infantile-onset cases.BMC gastroenterology · 2025Pooled it
- Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review.Clinical and experimental immunology · 2021Pooled it
- Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: a systematic review.Cancer immunology, immunotherapy : CII · 2021Pooled it
- Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study.Frontiers in immunology · 2021Pooled it
- Inhibitory receptor profiles for joint prediction of benefit and toxicity in immune checkpoint blockade.iScience · 2026Review
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Article
- A homozygous CTLA-4 variant causes CTLA-4 deficiency with severe immune dysregulation.Journal of human immunity · 2026Article
- Autosomal recessive human CTLA-4 deficiency with autoimmune infiltration.Journal of human immunity · 2026Article
- Beyond B cells: T and Innate Immune Mechanisms of Autoimmunity in Common Variable Immunodeficiency.Clinical reviews in allergy & immunology · 2026Review
- Multifocal HPV16-positive squamous cell carcinomas in CTLA-4 haploinsufficiency: expanding the spectrum of virus-associated malignancies.Immunologic research · 2026Article
- Immune Checkpoint Inhibitor-Associated Inflammatory Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Review
- Microbial engraftment and immune regulation during fecal microbiota transplantation and immune checkpoint inhibitor therapy.Nature communications · 2026Review
- A Flow Cytometry-Based Assay to Quantify the Binding of Transmembrane Ligands to Their Cognate Receptors Using Fluorescent Virus-Like Particles.Bio-protocol · 2026Article
- Clinical Spectrum and Therapeutic Options in Monogenic CTLA-4-, LRBA-, or SOCS1-Related Primary Immune Regulatory Disorders.The journal of allergy and clinical immunology. In practice · 2026Review
- A novel linker region truncating variant in BCL10 underlies a leaky immunodeficiency phenotype.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- The Treg-cell death axis in lung cancer: implications for immune evasion and novel therapeutic strategies.Molecular cancer · 2026Review
- Review
- A flow cytometry-based assay to quantify the binding of transmembrane ligands to their cognate receptors using fluorescent virus-like particles.bioRxiv : the preprint server for biology · 2026Article
- ILC2s and their immune checkpoints in the antitumor response.Journal for immunotherapy of cancer · 2026Review
394 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
40 authors at 10 institutions in 5 countries.
Funding
Abstract
The protein cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of immune responses, and its loss causes fatal autoimmunity in mice. We studied a large family in which five individuals presented with a complex, autosomal dominant immune dysregulation syndrome characterized by hypogammaglobulinemia, recurrent infections and multiple autoimmune clinical features. We identified a heterozygous nonsense mutation in exon 1 of CTLA4. Screening of 71 unrelated patients with comparable clinical phenotypes identified five additional families (nine individuals) with previously undescribed splice site and missense mutations in CTLA4. Clinical penetrance was incomplete (eight adults of a total of 19 genetically proven CTLA4 mutation carriers were considered unaffected). However, CTLA-4 protein expression was decreased in regulatory T cells (Treg cells) in both patients and carriers with CTLA4 mutations. Whereas Treg cells were generally present at elevated numbers in these individuals, their suppressive function, CTLA-4 ligand binding and transendocytosis of CD80 were impaired. Mutations in CTLA4 were also associated with decreased circulating B cell numbers. Taken together, mutations in CTLA4 resulting in CTLA-4 haploinsufficiency or impaired ligand binding result in disrupted T and B cell homeostasis and a complex immune dysregulation syndrome.
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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.