ArticleGut2015
Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4.
Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- Spleen volume in relation to ulcerative colitis and Crohn's disease: a Mendelian randomization study.Scientific reports · 2025Pooled it
- Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2020Guideline
- Gastroenterological disease detection using transformer-based medical imaging for sustainable healthcare.Scientific reports · 2026Article
- Where is the data? Delayed and chronic irAE surveillance and management after cessation of ICIs: expert insights from SITC on survivorship care and the need for long-term data.Journal for immunotherapy of cancer · 2026Article
- Novel pathogenicFrontiers in immunology · 2026Article
- Article
- Identification and impact of microbiota-derived metabolites in ascites of ovarian and gastrointestinal cancer.Cancer & metabolism · 2025Article
- Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases.FEBS letters · 2025Review
- Review
- Review
- CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner.Nature communications · 2024Article
- Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn's disease.Clinical and experimental immunology · 2024Observational
- Autoimmunity in Primary Immunodeficiencies (PID).Clinical reviews in allergy & immunology · 2023Review
- Pharmacologic Management of Monogenic and Very Early Onset Inflammatory Bowel Diseases.Pharmaceutics · 2023Review
- The ABACHAI clinical trial protocol: Safety and efficacy of abatacept (s.c.) in patients with CTLA-4 insufficiency or LRBA deficiency: A non controlled phase 2 clinical trial.Contemporary clinical trials communications · 2022Article
- Localization and movement of Tregs in gastrointestinal tract: a systematic review.Inflammation and regeneration · 2022Review
- Therapeutic gene editing of T cells to correct CTLA-4 insufficiency.Science translational medicine · 2022Article
- Early DNA methylation changes in children developing beta cell autoimmunity at a young age.Diabetologia · 2022Article
- Linking Genetic Diagnosis to Therapeutic Approach in Very Early Onset Inflammatory Bowel Disease: Pharmacologic Considerations.Paediatric drugs · 2022Review
- Co-Inhibitory Molecules - Their Role in Health and Autoimmunity; Highlighted by Immune Related Adverse Events.Frontiers in immunology · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveIBD is a group of complex, systemic disorders associated with intestinal inflammation and extraintestinal manifestations. Recent studies revealed Mendelian forms of IBD, which contributed significantly to our understanding of disease pathogenesis and the heritability of IBD.
designWe performed exome sequencing in a family with Crohn's disease (CD) and severe autoimmunity, analysed immune cell phenotype and function in affected and non-affected individuals, and performed in silico and in vitro analyses of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) structure and function.
resultsA novel missense variant was identified in CTLA4 encoding CTLA-4, a coinhibitory protein expressed by T cells and required for regulation of T cell activation. The residue affected by the mutation, CTLA-4 Tyr60, is evolutionarily highly conserved, and the identified Y60C variant is predicted to affect protein folding and structural stability and demonstrated to cause impaired CTLA-4 dimerisation and CD80 binding. Intestinal inflammation and autoimmunity in carriers of CTLA-4 Y60C exhibit incomplete penetrance with a spectrum of clinical presentations ranging from asymptomatic carrier status to fatal autoimmunity and intestinal inflammation. In a clinically affected CTLA-4 Y60C carrier, T cell proliferation was increased in vitro and associated with an increased ratio of memory to naive T cells in vivo, consistent with impaired regulation of T cell activation.
conclusionsOur results support the concept that variants in CTLA4 provide the basis for a novel Mendelian form of early-onset CD associated with systemic autoimmunity. Incomplete penetrance of autoimmunity further indicates the presence of other genetic and/or environmental modifiers.
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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.