ArticleThe Journal of allergy and clinical immunology2013
Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis.
Article in The Journal of allergy and clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis 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.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.
- Risk Factors for Disseminated Coccidioidomycosis, United States.Emerging infectious diseases · 2017Pooled it
- A digenic human immunodeficiency characterized by IFNAR1 and IFNGR2 mutations.The Journal of clinical investigation · 2017Trial
- Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026Review
- Genetic and transcriptomic determinants of disseminated coccidioidomycosis identify a founder variant inmedRxiv : the preprint server for health sciences · 2026Article
- Reactive and therapy induced bone marrow changes linked to systemic infectious and non-infectious disorders including MAS/HLH report from the European association for haematopathology, Dubrovnik 2024.Virchows Archiv : an international journal of pathology · 2026Article
- Th2 skewing in patients with disseminated coccidioidomycosis.JCI insight · 2026Article
- Interferon-γ Therapy in Patients With Refractory Disseminated Coccidioidomycosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Review
- Clinical and Immunological Impact of JAK Inhibition in Concurrent Down Syndrome and STAT1 Gain of Function.Journal of clinical immunology · 2025Article
- Type-2 immune skewing in patients with disseminated coccidioidomycosis.medRxiv : the preprint server for health sciences · 2025Article
- Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000-2025).Journal of fungi (Basel, Switzerland) · 2025Review
- A Child with Chronic Mucocutaneous Candidiasis Harbors a Novel Gain-of-Function Mutation in STAT1.Journal of clinical immunology · 2025Article
- Back With Vengeance: Delayed Gastrointestinal Sequelae of Histoplasmosis in a Patient With STAT3 Hyper-IgE Syndrome.ACG case reports journal · 2025Article
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- An activatingScience immunology · 2025Article
- Coccidioidomycosis: a growing global concern.The Journal of antimicrobial chemotherapy · 2025Review
- Prolonged STAT1 signaling in neurons causes hyperactive behavior.Brain, behavior, and immunity · 2025Article
- Genetics of progressive multifocal leukoencephalopathy: update on case reports with an inborn error of immunity and risk variants found in drug-linked cases.Frontiers in neurology · 2025Review
- A case displaying the importance of JAK1 and JAK2 gene transcription in antifungal defense against coccidioidomycosis.Frontiers in medicine · 2025Review
- Genetic causes of primary immunodeficiency in the Jordanian population.Biomedical reports · 2024Article
- Infections in Inborn Errors of STATs.Pathogens (Basel, Switzerland) · 2024Review
77 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
35 authors at 11 institutions in 5 countries.
Funding
Abstract
backgroundImpaired signaling in the IFN-γ/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis.
objectiveWe sought to identify the molecular defect in patients with disseminated dimorphic yeast infections.
methodsPBMCs, EBV-transformed B cells, and transfected U3A cell lines were studied for IFN-γ/IL-12 pathway function. STAT1 was sequenced in probands and available relatives. Interferon-induced STAT1 phosphorylation, transcriptional responses, protein-protein interactions, target gene activation, and function were investigated.
resultsWe identified 5 patients with disseminated Coccidioides immitis or Histoplasma capsulatum with heterozygous missense mutations in the STAT1 coiled-coil or DNA-binding domains. These are dominant gain-of-function mutations causing enhanced STAT1 phosphorylation, delayed dephosphorylation, enhanced DNA binding and transactivation, and enhanced interaction with protein inhibitor of activated STAT1. The mutations caused enhanced IFN-γ-induced gene expression, but we found impaired responses to IFN-γ restimulation.
conclusionGain-of-function mutations in STAT1 predispose to invasive, severe, disseminated dimorphic yeast infections, likely through aberrant regulation of IFN-γ-mediated inflammation.
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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.