Trial reportThe Journal of clinical investigation2017
A digenic human immunodeficiency characterized by IFNAR1 and IFNGR2 mutations.
Trial report in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Successful Hematopoietic Stem Cell Transplantation in a Patient with Complete IFN-γ Receptor 2 Deficiency: a Case Report and Literature Review.Journal of clinical immunology · 2020Pooled it
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- A Novel Case of IFNAR1 Deficiency Identified a Common Canonical Splice Site Variant in DOCK8 in Western Polynesia: The Importance of Validating Variants of Unknown Significance in Under-Represented Ancestries.Journal of clinical immunology · 2024Article
- Multiple inborn errors of type I IFN immunity in a 33-year-old male with a fatal case of COVID-19.Heliyon · 2024Article
- Evaluation of Genetic or Cellular Impairments in Type I IFN Immunity in a Cohort of Young Adults with Critical COVID-19.Journal of clinical immunology · 2024Article
- Review
- Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome.Journal of clinical immunology · 2022Article
- X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia.Journal of clinical immunology · 2022Article
- Host-Pathogen Interactions Operative duringImmune network · 2021Review
- Differential roles of interferons in innate responses to mucosal viral infections.Trends in immunology · 2021Review
- Identifying digenic disease genes via machine learning in the Undiagnosed Diseases Network.American journal of human genetics · 2021Article
- Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Genetic Mosaicism as a Cause of Inborn Errors of Immunity.Journal of clinical immunology · 2021Review
- Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency.The Journal of clinical investigation · 2021Article
- Genetic Lesions of Type I Interferon Signalling in Human Antiviral Immunity.Trends in genetics : TIG · 2021Review
- High Dose IFN-Frontiers in immunology · 2021Article
- Genetic influences on viral-induced cytokine responses in the lung.Mucosal immunology · 2021Review
- Early type I IFN blockade improves the efficacy of viral vaccines.The Journal of experimental medicine · 2020Article
- Article
- Incomplete penetrance in primary immunodeficiency: a skeleton in the closet.Human genetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Primary immunodeficiencies are often monogenic disorders characterized by vulnerability to specific infectious pathogens. Here, we performed whole-exome sequencing of a patient with disseminated Mycobacterium abscessus, Streptococcus viridians bacteremia, and cytomegalovirus (CMV) viremia and identified mutations in 2 genes that regulate distinct IFN pathways. The patient had a homozygous frameshift deletion in IFNGR2, which encodes the signal transducing chain of the IFN-γ receptor, that resulted in minimal protein expression and abolished downstream signaling. The patient also harbored a homozygous deletion in IFNAR1 (IFNAR1*557Gluext*46), which encodes the IFN-α receptor signaling subunit. The IFNAR1*557Gluext*46 resulted in replacement of the stop codon with 46 additional codons at the C-terminus. The level of IFNAR1*557Gluext*46 mutant protein expressed in patient fibroblasts was comparable to levels of WT IFNAR1 in control fibroblasts. IFN-α-induced signaling was impaired in the patient fibroblasts, as evidenced by decreased STAT1/STAT2 phosphorylation, nuclear translocation of STAT1, and expression of IFN-α-stimulated genes critical for CMV immunity. Pretreatment with IFN-α failed to suppress CMV protein expression in patient fibroblasts, whereas expression of WT IFNAR1 restored IFN-α-mediated suppression of CMV. This study identifies a human IFNAR1 mutation and describes a digenic immunodeficiency specific to type I and type II IFNs.
Indexed as
Identifiers
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.