Observational studyThe Journal of clinical investigation2020
Haploinsufficiency of immune checkpoint receptor CTLA4 induces a distinct neuroinflammatory disorder.
Observational study in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 18 papers.
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.
Detection and Characterization of Host Defense Defects
Neurologic and Immunologic Characteristics of CTLA-4 and LRBA Hereditary Deficiency
Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- 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
- Antigen Microarray Reveals Broad and Subclinical Autoimmunity in Patients with Inborn Errors of Immunity.Journal of clinical immunology · 2026Article
- Two Cases of CLIPPERS-like Syndrome Sharing a Hypomorphic UNC13D Variant.Journal of clinical immunology · 2026Article
- Diagnostic clues in patients with clinical malabsorption and pathological small intestinal villous atrophy: Immune-mediated type and beyond.World journal of gastroenterology · 2026Review
- Neuroinflammation in CTLA-4 Haploinsufficiency: Case Report of a New Variant with Remarkable Response to Targeted Therapy.International journal of molecular sciences · 2025Article
- Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.Clinical reviews in allergy & immunology · 2025Article
- Review
- Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Clinical Challenges of Emerging Acquired Autoinflammatory Diseases, Including VEXAS Syndrome.Internal medicine (Tokyo, Japan) · 2025Review
- Management of Autoimmune Encephalitis in a 7-Year-Old Child With CTLA-4 Haploinsufficiency and AMPA Receptor Antibodies: A Case Report.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Clinical, Radiologic, and Immunologic Features of Patients With CTLA4 Deficiency With Neurologic Involvement.Neurology · 2023Observational
- Origins and immunopathogenesis of autoimmune central nervous system disorders.Nature reviews. Neurology · 2023Review
- Editorial: Women in primary immunodeficiencies.Frontiers in immunology · 2023Article
- Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR.Journal for immunotherapy of cancer · 2021Review
- Challenging Mimickers in the Diagnosis of Sarcoidosis: A Case Study.Diagnostics (Basel, Switzerland) · 2021Article
- Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease.JCI insight · 2021Article
- Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUNDCytotoxic T lymphocyte antigen 4 (CTLA4) is essential for immune homeostasis. Genetic mutations causing haploinsufficiency (CTLA4h) lead to a phenotypically heterogenous, immune-mediated disease that can include neuroinflammation. The neurological manifestations of CTLA4h are poorly characterized.METHODSWe performed an observational natural history study of 50 patients with CTLA4h who were followed at the NIH. We analyzed clinical, radiological, immunological, and histopathological data.RESULTSEvidence for neuroinflammation was observed in 32% (n = 16 of 50) of patients in this cohort by magnetic resonance imaging (MRI) and/or by cerebrospinal fluid analysis. Clinical symptoms were commonly absent or mild in severity, with headaches as the leading complaint (n = 13 of 16). The most striking findings were relapsing, large, contrast-enhancing focal lesions in the brain and spinal cord observed on MRI. We detected inflammation in the cerebrospinal fluid and leptomeninges before the parenchyma. Brain biopsies of inflammatory lesions from 10 patients showed perivascular and intraparenchymal mixed cellular infiltrates with little accompanying demyelination or neuronal injury.CONCLUSIONSNeuroinflammation due to CTLA4h is mediated primarily by an infiltrative process with a distinct and striking dissociation between clinical symptoms and radiological findings in the majority of patients.FUNDINGNIAID, NIH, Division of Intramural Research, NINDS, NIH, Division of Intramural Research, and the National Multiple Sclerosis Society-American Brain Foundation.TRIAL REGISTRATIONClinicalTrials.gov NCT00001355.
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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.