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Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia.
Philippot, Quentin; Fekkar, Arnaud; Gervais, Adrian; Le Voyer, Tom; Boers, Leonoor S; Conil, Clément; Bizien, Lucy; de Brabander, Justin; Duitman, Jan Willem; Romano, Alessia; Rosain, Jérémie; Blaize, Marion; Migaud, Mélanie; Jeljeli, Maxime; Hammadi, Boualem; Desmons, Aurore; Marchal, Astrid; Mayaux, Julien; Zhang, Qian; Jouanguy, Emmanuelle; Borie, Raphael; Crestani, Bruno; Luyt, Charles Edouard; Adle-Biassette, Homa; Sene, Damien; Megarbane, Bruno; Cobat, Aurélie; Bastard, Paul; Bos, Lieuwe D J; Casanova, Jean-Laurent; Puel, Anne.
  • Philippot Q; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France. quentin.philippot@institutimagine.org.
  • Fekkar A; Imagine Institute, Université Paris Cité, Paris, EU, France. quentin.philippot@institutimagine.org.
  • Gervais A; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Le Voyer T; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Boers LS; AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, EU, France.
  • Conil C; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Bizien L; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • de Brabander J; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Duitman JW; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Romano A; Amsterdam UMC, University of Amsterdam, Intensive Care Medicine, Meibergdreef 9, Amsterdam, EU, The Netherlands.
  • Rosain J; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Blaize M; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Migaud M; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Jeljeli M; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Hammadi B; Center for Experimental Molecular Medicine, Amsterdam UMC, Amsterdam, EU, Netherlands.
  • Desmons A; Amsterdam UMC, Location AMC, Department of Pulmonary Medicine, University of Amsterdam, 1105 AZ, Amsterdam, EU, The Netherlands.
  • Marchal A; Amsterdam UMC, Department of Experimental Immunology, Location University of Amsterdam, 1105 AZ, Amsterdam, EU, The Netherlands.
  • Mayaux J; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Zhang Q; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Jouanguy E; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Borie R; AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, EU, France.
  • Crestani B; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Luyt CE; Imagine Institute, Université Paris Cité, Paris, EU, France.
  • Adle-Biassette H; Département 3I « Infection, Immunité Et Inflammation ¼, Institut Cochin, INSERM U1016, Université Paris Cité, Paris, EU, France.
  • Sene D; Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d'Immunologie Biologique, Université Paris Cité, Paris, EU, France.
  • Megarbane B; General Chemistry Laboratory, Department of Clinical Chemistry, APHP, Necker Hospital for Sick Children, Paris, EU, France.
  • Cobat A; Clinical Metabolomic Department, Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Saint Antoine Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP Sorbonne Université), Paris, France.
  • Bastard P; Laboratory of Human Genetics of Infectious Diseases, Imagine Institute for Genetic Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse 75015, EU, Paris, France.
  • Bos LDJ; Imagine Institute, Université Paris Cité, Paris, EU, France.
J Clin Immunol ; 2023 May 20.
Article in English | MEDLINE | ID: covidwho-2325547
ABSTRACT
Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% of unvaccinated patients with life-threatening COVID-19 pneumonia. We report here the presence of auto-Abs neutralizing type I IFNs in the bronchoalveolar lavage (BAL) of 54 of the 415 unvaccinated patients (13%) with life-threatening COVID-19 pneumonia tested. The 54 individuals with neutralizing auto-Abs in the BAL included 45 (11%) with auto-Abs against IFN-α2, 37 (9%) with auto-Abs against IFN-ω, 54 (13%) with auto-Abs against IFN-α2 and/or ω, and five (1%) with auto-Abs against IFN-ß, including three (0.7%) with auto-Abs neutralizing IFN-α2, IFN-ω, and IFN-ß, and two (0.5%) with auto-Abs neutralizing IFN-α2 and IFN-ß. Auto-Abs against IFN-α2 also neutralize the other 12 subtypes of IFN-α. Paired plasma samples were available for 95 patients. All seven patients with paired samples who had detectable auto-Abs in BAL also had detectable auto-Abs in plasma, and one patient had auto-Abs detectable only in blood. Auto-Abs neutralizing type I IFNs are, therefore, present in the alveolar space of at least 10% of patients with life-threatening COVID-19 pneumonia. These findings suggest that these auto-Abs impair type I IFN immunity in the lower respiratory tract, thereby contributing to hypoxemic COVID-19 pneumonia.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2023 Document Type: Article Affiliation country: S10875-023-01512-9

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2023 Document Type: Article Affiliation country: S10875-023-01512-9