Correction: Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency

Campbell, Tessa Mollie; Li, Yong; Zhang, Qian; Moncada-Vélez, Marcela; Covill, Laura; Zhang, Peng; Darazam, Ilad Alavi; Bastard, Paul; Bizien, Lucy; Bucciol, Giorgia; Enoksson, Sara Lind; Jouanguy, Emmanuelle; Khan, Taushif; Kendir-Demirkol, Yasemin; Arias, Andrés A.; Mansouri, Davood; Marits, Per; Marr, Nico; Migeotte, Isabelle; Moens, Leen; Özçelık, Tayfun; Pellier, Isabelle; Sendel, Anton; Şenoğlu, Sevtap; Shahrooei, Mohammad; Smith, C. I. Edvard; Vandernoot, Isabelle; Willekens, Karen; Yaşar, Kadriye Kart; Bergman, Peter; Abel, Laurent; Cobat, Aurélie; Casanova, Jean‐Laurent; Meyts, Isabelle; Bryceson, Yenan T.

doi:10.1084/jem.2022020210282022c

Cited by 11 publications

(10 citation statements)

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“…An AR deficiency in IRF7, a key transcriptional regulator of type I IFNs, was first reported in a 3-year-old child with critical influenza pneumonia ( 42 ). AR IRF7 deficiency was recently reported in six other patients from five families ( 43 ). Intriguingly, the viral infection phenotype of these patients was restricted to the respiratory tract ( Table 1 ).…”

Section: Inborn Errors Of Type I Ifn Immunity To Virusesmentioning

confidence: 89%

“…Two unrelated adults were found to have AR IFNAR1 deficiency, while another two had AR IRF7 deficiency ( 23 ). Other patients with critical COVID-19 due to AR IFNAR1 ( 16 , 24 , 25 ) or AR IRF7 ( 43 ) deficiency were later reported, as well as a patient with AR TBK1 deficiency ( 128 ). Remarkably, the young and even middle-aged adults with such profound AR deficits identified had remained well until they developed COVID-19.…”

Section: Critical Covid-19 Pneumonia and Type I Ifn Deficiencymentioning

confidence: 98%

“…It is possible that residual IFN-β levels account for the better control of viruses in these patients than in patients with IFNAR1 or IFNAR2 deficiency, despite the lack of IRF7-dependent induction of type I and III IFNs. Adaptive immunity to viruses may also compensate for the defects of type I IFN immunity in these patients ( 43 ). In contrast, a child with an autosomal dominant (AD) and partial form of IRF3 deficiency has been reported to have HSE ( 44 ).…”

Section: Inborn Errors Of Type I Ifn Immunity To Virusesmentioning

confidence: 99%

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Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Casanova¹,

Anderson²

2023

Journal of Clinical Investigation

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Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying a few severe viral illnesses. Autoantibodies neutralizing type I IFNs due to rare inborn errors of autoimmune regulator (AIRE)–driven T cell tolerance were discovered in 2006, but not initially linked to any viral disease. These two lines of clinical investigation converged in 2020, with the discovery that inherited and/or autoimmune deficiencies of type I IFN immunity accounted for approximately 15%–20% of cases of critical COVID-19 pneumonia in unvaccinated individuals. Thus, insufficient type I IFN immunity at the onset of SARS-CoV-2 infection may be a general determinant of life-threatening COVID-19. These findings illustrate the unpredictable, but considerable, contribution of the study of rare human genetic diseases to basic biology and public health.

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Section: Inborn Errors Of Type I Ifn Immunity To Virusesmentioning

confidence: 89%

Section: Critical Covid-19 Pneumonia and Type I Ifn Deficiencymentioning

confidence: 98%

Section: Inborn Errors Of Type I Ifn Immunity To Virusesmentioning

confidence: 99%

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Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Casanova¹,

Anderson²

2023

Journal of Clinical Investigation

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“…Based on local availability, research or clinical next-generation sequencing of the genomic DNA was performed using either whole exome or a targeted panel approach (as described previously; Béziat et al, 2021;Campbell et al, 2022;Chovanec et al, 2022;Hebert et al, 2022;Murrell et al, 2022;Tarailo-Graovac et al, 2016). After bioinformatic analysis, de novo and inherited STAT6 variants that were predicted to be damaging and that segregated with disease were identified in each family (Tables S4 and S5).…”

Section: Identification Of Stat6 Variant Via Next-generation Sequencingmentioning

confidence: 99%

Human germline heterozygous gain-of-functionSTAT6variants cause severe allergic disease

Sharma

Leung

Momenilandi

et al. 2023

Journal of Experimental Medicine

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STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti–IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

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“…Inborn errors of type I interferon (IFN) immunity have been identified by two complementary approaches in about 1%-5% of cases. A candidategene approach focusing on genes for which mutations had previously been shown to underlie critical influenza pneumonia [71,72] revealed inborn errors of TLR3-and IRF7-dependent type I IFN immunity [73,74] (Fig. 2).…”

Section: Sars-cov-2 and Associated Diseasesmentioning

confidence: 99%

Human genetic and immunological determinants of SARS‐CoV‐2 and Epstein–Barr virus diseases in childhood: Insightful contrasts

Pan‐Hammarström

Casanova

2023

J Intern Med

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There is growing evidence to suggest that severe disease in children infected with common viruses that are typically benign in other children can result from inborn errors of immunity or their phenocopies. Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a cytolytic respiratory RNA virus, can lead to acute hypoxemic COVID‐19 pneumonia in children with inborn errors of type I interferon (IFN) immunity or autoantibodies against IFNs. These patients do not appear to be prone to severe disease during infection with Epstein–Barr virus (EBV), a leukocyte‐tropic DNA virus that can establish latency. By contrast, various forms of severe EBV disease, ranging from acute hemophagocytosis to chronic or long‐term illnesses, such as agammaglobulinemia and lymphoma, can manifest in children with inborn errors disrupting specific molecular bridges involved in the control of EBV‐infected B cells by cytotoxic T cells. The patients with these disorders do not seem to be prone to severe COVID‐19 pneumonia. These experiments of nature reveal surprising levels of redundancy of two different arms of immunity, with type I IFN being essential for host defense against SARS‐CoV‐2 in respiratory epithelial cells, and certain surface molecules on cytotoxic T cells essential for host defense against EBV in B lymphocytes.

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Correction: Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency

Cited by 11 publications

References 0 publications

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Human germline heterozygous gain-of-functionSTAT6variants cause severe allergic disease

Human genetic and immunological determinants of SARS‐CoV‐2 and Epstein–Barr virus diseases in childhood: Insightful contrasts

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