ReviewJournal of clinical immunology2020
Human STAT1 Gain-of-Function Heterozygous Mutations: Chronic Mucocutaneous Candidiasis and Type I Interferonopathy.
Review in Journal of clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 3 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
107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- Pooled it
- The T385M STAT1 gain-of-function mutation confers the most severe disease outcomes.Frontiers in immunology · 2025Pooled it
- Clinical Relevance of Gain- and Loss-of-Function Germline Mutations in STAT1: A Systematic Review.Frontiers in immunology · 2021Pooled it
- Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity.Frontiers in immunology · 2022Trial
- JAK-inhibitor treatment induces rapid yet incomplete immune reconstitution in STAT1 gain-of-function.Journal of human immunity · 2026Article
- STAT1 gain-of-function in 12 Moroccan patients: Clinical and genetic insights.Journal of human immunity · 2026Article
- Immune Dysregulation in Down Syndrome: Implications for Infectious Susceptibility and Vaccine Response.Journal of clinical immunology · 2026Review
- Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026Review
- Kat5 deficiency in alveolar type II cells licenses STAT6-driven glycolytic reprogramming and pulmonary fibrosis.Nature communications · 2026Article
- Genetic mechanisms underlying host susceptibility to central nervous system viral infections.Current opinion in infectious diseases · 2026Review
- The host immune response to Mycobacterium tuberculosis determining protection or disease progression.Nature immunology · 2026Review
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- Rhino-orbito-cerebral Rhizopus delemar infection in a patient with anti-melanoma differentiation-associated-5-positive dermatomyositis diagnosed by metagenomic next-generation sequencing: a case report.BMC infectious diseases · 2026Article
- Variation in antiviral immunity and inflammation pathways precedes HIV-1 infection in a high-risk African cohort.The Journal of clinical investigation · 2026Article
- A Clinical Prediction Model for Invasive Pulmonary Fungal Disease in Dialysis Patients: Development, Validation, and Pharmacist-Led Application.Infection and drug resistance · 2026Article
- RNA-Seq of Cultured Peripheral Blood Lymphocytes Improves Identification of Cryptic Splicing Defects in Rare Disease Diagnostics.Human mutation · 2026Article
- Second-order regulation: IFN-γ suppresses IL-17A-mediated type 3 inflammation.Frontiers in immunology · 2026Article
- STAT1-L351F is associated with enhanced interferon signaling and susceptibility toFrontiers in immunology · 2026Article
- In silico modeling guides identification of novel JAK1 variants associated with immune dysregulation.EMBO molecular medicine · 2025Article
- Investigation of the transcriptional impact of rare germline JAK/STAT variants found in a Tyrolean alpine community.BMC genomics · 2025Article
47 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
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Heterozygous gain-of-function (GOF) mutations in STAT1 in patients with chronic mucocutaneous candidiasis (CMC) and hypothyroidism were discovered in 2011. CMC is the recurrent or persistent mucocutaneous infection by Candida fungi, and hypothyroidism results from autoimmune thyroiditis. Patients with these diseases develop other infectious diseases, including viral, bacterial, and fungal diseases, and other autoimmune manifestations, including enterocolitis, immune cytopenia, endocrinopathies, and systemic lupus erythematosus. STAT1-GOF mutations are highly penetrant with a median age at onset of 1 year and often underlie an autosomal dominant trait. As many as 105 mutations at 72 residues, including 65 recurrent mutations, have already been reported in more than 400 patients worldwide. The GOF mechanism involves impaired dephosphorylation of STAT1 in the nucleus. Patient cells show enhanced STAT1-dependent responses to type I and II interferons (IFNs) and IL-27. This impairs Th17 cell development, which accounts for CMC. The pathogenesis of autoimmunity likely involves enhanced type I IFN responses, as in other type I interferonopathies. The pathogenesis of other infections, especially those caused by intramacrophagic bacteria and fungi, which are otherwise seen in patients with diminished type II IFN immunity, has remained mysterious. The cumulative survival rates of patients with and without severe disease (invasive infection, cancer, and/or symptomatic aneurysm) at 60 years of age are 31% and 87%, respectively. Severe autoimmunity also worsens the prognosis. The treatment of patients with STAT1-GOF mutations who suffer from severe infectious and autoimmune manifestations relies on hematopoietic stem cell transplantation and/or oral JAK inhibitors.
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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.