ArticleJournal of clinical immunology2020
Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome.
Article 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 54 papers, 1 of them a synthesis that pooled it.
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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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Revisiting down syndrome through the lens of interferonopathy and innate immune dysregulation.Frontiers in immunology · 2026Pooled it
- Trial
- Fulminant Secondary HLH Following EBV Reactivation in an Adult With Trisomy 21 After Teplizumab Treatment for Stage 2 Type 1 Diabetes.Diabetes care · 2026Article
- Spatially resolved multiomics of human meningeal development reveal lineage and disease dynamics.Nature cell biology · 2026Article
- Clinical considerations for immune dysregulation and immunodeficiency in Down syndrome.Journal of human immunity · 2026Review
- Imaging findings in pediatric interferonopathies.Pediatric radiology · 2026Review
- Immune Dysregulation in Down Syndrome: Implications for Infectious Susceptibility and Vaccine Response.Journal of clinical immunology · 2026Review
- How I Treat: Immune dysregulation in Down syndrome.Journal of human immunity · 2026Review
- Surveying immune and inflammatory alterations in periodontitis among individuals with Down syndrome: A preliminary cross-sectional study.Journal of periodontology · 2026Article
- Toward a monogenic architecture of human infections: From 1996 to 2026.Journal of human immunity · 2026Review
- Article
- Periodontitis and Alzheimer's disease, common pathways in down syndrome.Frontiers in dental medicine · 2026Review
- Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome.Frontiers in immunology · 2026Article
- Article
- Down Syndrome Alters Type III IFN and Proinflammatory Airway Epithelial Responses to Respiratory Syncytial Virus Infection.American journal of respiratory cell and molecular biology · 2025Article
- Article
- Clinical and Immunological Impact of JAK Inhibition in Concurrent Down Syndrome and STAT1 Gain of Function.Journal of clinical immunology · 2025Article
- Emapalumab as a Life-Saving Therapy for Macrophage Activation Syndrome in Refractory Systemic Juvenile Idiopathic Arthritis with Trisomy 21.Turkish archives of pediatrics · 2025Article
- Type I interferon signalling and interferon-responsive microglia in health and disease.The FEBS journal · 2025Review
- Accelerated Tempo of Cortical Neurogenesis in Down Syndrome.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 5 countries.
Funding
Abstract
Down syndrome (DS) is characterized by the occurrence of three copies of human chromosome 21 (HSA21). HSA21 contains a cluster of four interferon receptor (IFN-R) genes: IFNAR1, IFNAR2, IFNGR2, and IL10RB. DS patients often develop mucocutaneous infections and autoimmune diseases, mimicking patients with heterozygous gain-of-function (GOF) STAT1 mutations, which enhance cellular responses to three types of interferon (IFN). A gene dosage effect at these four loci may contribute to the infectious and autoimmune manifestations observed in individuals with DS. We report high levels of IFN-αR1, IFN-αR2, and IFN-γR2 expression on the surface of monocytes and EBV-transformed-B (EBV-B) cells from studying 45 DS patients. Total and phosphorylated STAT1 (STAT1 and pSTAT1) levels were constitutively high in unstimulated and IFN-α- and IFN-γ-stimulated monocytes from DS patients but lower than those in patients with GOF STAT1 mutations. Following stimulation with IFN-α or -γ, but not with IL-6 or IL-21, pSTAT1 and IFN-γ activation factor (GAF) DNA-binding activities were significantly higher in the EBV-B cells of DS patients than in controls. These responses resemble the dysregulated responses observed in patients with STAT1 GOF mutations. Concentrations of plasma type I IFNs were high in 12% of the DS patients tested (1.8% in the healthy controls). Levels of type I IFNs, IFN-Rs, and STAT1 were similar in DS patients with and without recurrent skin infections. We performed a genome-wide transcriptomic analysis based on principal component analysis and interferon modules on circulating monocytes. We found that DS monocytes had levels of both IFN-α- and IFN-γ-inducible ISGs intermediate to those of monocytes from healthy controls and from patients with GOF STAT1 mutations. Unlike patients with GOF STAT1 mutations, patients with DS had normal circulating Th17 counts and a high proportion of terminally differentiated CD8
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