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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.

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. Imagine Institute, Université Paris Cité, Paris, EU, France. quentin.philippot@institutimagine.org. 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. Imagine Institute, Université Paris Cité, Paris, EU, France. AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, EU, France. Amsterdam UMC, University of Amsterdam, Intensive Care Medicine, Meibergdreef 9, Amsterdam, EU, The Netherlands. Center for Experimental Molecular Medicine, Amsterdam UMC, Amsterdam, EU, Netherlands. Amsterdam UMC, Location AMC, Department of Pulmonary Medicine, University of Amsterdam, 1105 AZ, Amsterdam, EU, The Netherlands. Amsterdam UMC, Department of Experimental Immunology, Location University of Amsterdam, 1105 AZ, Amsterdam, EU, The Netherlands. Amsterdam Infection & Immunity, Inflammatory Diseases, 1105 AZ, Amsterdam, EU, The Netherlands. Département 3I « Infection, Immunité Et Inflammation », Institut Cochin, INSERM U1016, Université Paris Cité, Paris, EU, France. Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d'Immunologie Biologique, Université Paris Cité, Paris, EU, France. General Chemistry Laboratory, Department of Clinical Chemistry, APHP, Necker Hospital for Sick Children, Paris, EU, France. 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. INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, EU, France. Site Pitié-Salpêtrière, Service de Pneumologie, Médecine Intensive et Réanimation, Département R3S, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, EU, France. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA. Service de Pneumologie A Hôpital Bichat, APHP, Paris, EU, France. Inserm, PHERE, Université Paris Cité, 75018, Paris, EU, France. Service de Médecine Intensive Réanimation, Institut de Cardiologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, EU, France. Inserm, Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, EU, France. AP-HP, Hôpital Lariboisière, Service Anatomie Pathologique and Université de Paris, Paris, EU, France. Inserm, NeuroDiderot, Paris, EU, France. Internal Medicine Department, AP-HP, Lariboisière Hospital, Paris, EU, France. Université Paris Cité, Paris, EU, France. Department of Medical and Toxicological Critical Care, APHP, Lariboisière Hospital, Paris, EU, France. INSERM UMRS-1144, Paris-University, Paris, EU, France. Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France. Department of Pediatrics, Necker Hospital for Sick Children, Paris, EU, France. Howard Hughes Medical Institute, New York, NY, USA.

Journal of clinical immunology. 2023;(6):1093-1103
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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-β, including three (0.7%) with auto-Abs neutralizing IFN-α2, IFN-ω, and IFN-β, and two (0.5%) with auto-Abs neutralizing IFN-α2 and IFN-β. 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.