ArticleThe Journal of experimental medicine2021
Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
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Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.
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181citing papers in PubMed
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181 citing papers in PubMed, 301 citations in OpenAlex.
- Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.Influenza and other respiratory viruses · 2023Trial
- SARS-CoV-2 Spike Protein-Directed Monoclonal Antibodies May Ameliorate COVID-19 Complications in APECED Patients.Frontiers in immunology · 2021Trial
- Autoantibodies neutralizing type I interferons in COVID-19 patients from southern Brazil.Journal of human immunity · 2026Article
- High prevalence of autoantibodies neutralizing type I IFNs in Japanese patients with hepatitis C.Journal of human immunity · 2026Article
- High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Anti-Type I Interferon Autoantibodies in COVID-19 and Systemic Lupus Erythematosus: A Comparative Review.Antibodies (Basel, Switzerland) · 2026Review
- Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections.Cell · 2026Article
- Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts.Journal of human immunity · 2026Article
- High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies.medRxiv : the preprint server for health sciences · 2026Article
- CD4 T-cell platform for delivering interferons as an antiviral countermeasure with a focus on SARS-CoV-2.Molecular medicine (Cambridge, Mass.) · 2026Article
- Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis.The Journal of experimental medicine · 2026Article
- Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic contribution to severe COVID-19 in adults under 60 years without major comorbidities in the German National Pandemic Cohort Network (NAPKON).Human genomics · 2026Article
- The immune system as a regulator of normal physiology.Frontiers in immunology · 2026Review
- Human interferon-ω: an underappreciated type I interferon.Frontiers in immunology · 2026Review
- A novel heterozygous pathogenicJournal of human immunity · 2025Article
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- Revisiting the monocrotaline-treated rat as a model of inflammatory lung disease: COVID-19 and future pandemic threats?Animal models and experimental medicine · 2025Review
- Idiopathic inflammatory myopathies lack neutralising autoantibodies to type- I, II and III interferons.RMD open · 2025Observational
- Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts.medRxiv : the preprint server for health sciences · 2025Article
121 more citing papers are in PubMed but not listed here.
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Authors and funding
65 authors at 20 institutions in 9 countries.
Paul BastardLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Elizaveta OrlovaEndocrinology Research Centre, Moscow, Russia.
Leila SozaevaEndocrinology Research Centre, Moscow, Russia.
Romain LévyLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Alyssa JamesLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Monica M SchmittLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Sebastian OchoaLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Maria KarevaEndocrinology Research Centre, Moscow, Russia.
Yulia RodinaDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Adrian GervaisLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Tom Le VoyerLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Jérémie RosainLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Quentin PhilippotLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Anna-Lena NeehusLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Elana ShawLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Mélanie MigaudLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Lucy BizienLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Olov EkwallDepartment of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden.
Stefan BergDepartment of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden.
Guglielmo BeccutiDepartment of Medical Sciences, University of Turin, Turin, Italy.
Lucia GhizzoniDepartment of Medical Sciences, University of Turin, Turin, Italy.
Gérard ThiriezIntensive Care Unit, Besançon Hospital, Besançon, France.
Arthur PavotIntensive Care Unit, Kremlin-Bicêtre Hospital, Kremlin-Bicêtre, France.
Cécile GoujardInternal Medicine Department, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris, Paris Saclay University, Institut National de la Santé et de la Recherche Médicale U1018, Le Kremlin-Bicêtre, France.
Marie-Louise FrémondPediatric Immunology, Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris, Paris, France.
Edwin CarterCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, Edinburgh, UK.
Anya RothenbuhlerPediatric Endocrinology Department, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris, Paris Saclay University, Le Kremlin-Bicêtre, France.
Agnès LinglartPediatric Endocrinology Department, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris, Paris Saclay University, Le Kremlin-Bicêtre, France.
Brigite MignotPediatric Medicine Unit, University Hospital of Besançon, Besançon, France.
Aurélie ComtePediatric Medicine Unit, University Hospital of Besançon, Besançon, France.
Nathalie CheikhPediatric Hematology Unit, University Hospital of Besançon, Besançon, France.
Olivier HermineUniversity of Paris, Imagine Institute, Paris, France.
Lars BreivikDepartment of Clinical Science and K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway.
Eystein S HusebyeDepartment of Clinical Science and K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway.
Sébastien HumbertInternal Medicine Unit, Besançon Hospital, Besançon, France.
Pierre RohrlichPediatric Hematology and Oncology unit, Centre Hospitalier Universitaire de Nice, Nice, France.
Alain CoaquetteLaboratory of Virology, Besançon Hospital, Besançon, France.
Fanny VuotoInfectious Disease Unit, Lille Hospital, Lille, France.
Karine FaureInfectious Disease Unit, Lille Hospital, Lille, France.
Nizar MahlaouiPediatric Immunology, Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris, Paris, France.
Primož KotnikFaculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Tadej BattelinoFaculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Katarina Trebušak PodkrajšekFaculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Kai KisandInstitute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Elise M N FerréLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Thomas DiMaggioLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Lindsey B RosenLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Peter D BurbeloNational Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD.
Martin McIntyreRoyal Alexandra Hospital, Paisley, Scotland, UK.
Nelli Y KannDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Anna ShcherbinaDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Maria PavlovaDepartment of Endocrinology N°1, Sechenov University, Moscow, Russia.
Anna KolodkinaEndocrinology Research Centre, Moscow, Russia.
Steven M HollandLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Shen-Ying ZhangLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Yanick J CrowLaboratory of Neurogenetics and Neuroinflammation, Université de Paris, Imagine Institute, Paris, France.
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Helen C SuLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Laurent AbelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Mark S AndersonDiabetes Center, University of California, San Francisco, San Francisco, CA.
Emmanuelle JouanguyLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Bénédicte NevenUniversity of Paris, Imagine Institute, Paris, France.
Anne PuelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Jean-Laurent CasanovaLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
Michail S LionakisLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Inserm · FRNational Institutes of Health · USCentre Hospitalier Universitaire de Besançon · FREndocrinology Research Center · RUUniversité Paris Cité · FRDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology · RUUniversity of Ljubljana · SILille’s Cardiology Hospital · FRUniversité Paris-Saclay · FRUniversity of Gothenburg · SEUniversity of Turin · ITBicêtre Hospital · FRCentre de Référence Déficits Immunitaires Héréditaires · FRCentre Hospitalier Universitaire de Nice · FRHaukeland University Hospital · NOHoward Hughes Medical Institute · USMedical Research Council · GBRoyal Alexandra Hospital · GBSechenov University · RUUniversity of Bergen · NO
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MDeveloping, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MCharacterization of the cellular and molecular bases of inborn errors of immunityZIAAI001222 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2017 to 2025
$15.2MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MHost factors contributing to susceptibility to COVID-19 diseaseZIAAI001265 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2020 to 2025
$9.5MMonogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19R01AI088364 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova, Shen-Ying Zhang · 2010 to 2026
$8.7MNHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9MCharacterization of host immune responses to SARS-CoV-2ZIAAI001270 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2020 to 2025
$1.2MHigh Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890kThe pathogenesis of COVID-19ZIAAI001318 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LIONAKIS, MICHAIL · 2020 to 2023
$290kNCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR001866NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006504NIAID NIH HHS R01 AI088364NIH HHS S10 OD018521
Abstract
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
Indexed as
AdolescentAdultAutoantibodiesChildCOVID-19FemaleHumansInterferon Type IMaleMiddle AgedPneumoniaPolyendocrinopathies, AutoimmuneSARS-CoV-2Young AdultAutoantibodiesinterferon kappaInterferon Type I
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