SEARCHCOHORTimmunology, pulmonology

cohort·immunology, pulmonology, infectious disease, critical care, internal medicine·PMC10199445

Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia

Journal of Clinical Immunology · 31 authors, 28 centres

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TL;DR

This cohort study found that at least 10% of patients with life-threatening COVID-19 pneumonia have autoantibodies that neutralize type I interferons in their bronchoalveolar lavage fluid. The presence of these autoantibodies was not associated with differences in mortality or the degree of alveolar inflammation measured by 59 biomarkers.

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The study investigated the presence and impact of autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in the lower respiratory tract of patients with life-threatening COVID-19 pneumonia. Researchers tested bronchoalveolar lavage (BAL) samples and found auto-Abs neutralizing high concentrations of type I IFNs in at least 10% of patients. In paired samples, all patients with BAL auto-Abs also had them in plasma. A key analysis compared 11 patients with BAL auto-Abs against 117 without them. Mortality and length of ICU stay were similar between these groups. Principal component analysis and measurement of 59 inflammatory biomarkers in the BAL revealed no major differences in alveolar inflammation profiles, with only three biomarkers (MIP1α, MIP1β, and TRAIL) showing significantly higher concentrations in the auto-Ab-positive group. The authors suggest these auto-Abs likely impair local type I IFN immunity and contribute to pneumonia development, representing a general pathogenic mechanism.

STUDY TYPE

cohort

SPECIALTY

immunology

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ORIGINAL PAPER

PMC10199445

Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia

Journal of Clinical Immunology

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ABSTRACT

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. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-023-01512-9. Keywords: COVID-19, SARS-CoV-2, Cytokines, Type I interferons

CITATION EXPORT

Quentin Philippot, Arnaud Fekkar, Adrian Gervais et al.. Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia. Journal of Clinical Immunology. (2023). https://doi.org/10.1007/s10875-023-01512-9

AUTHORS

31 · 28 CENTRES

Quentin Philippot, Arnaud Fekkar, Adrian Gervais, Tom Le Voyer, Leonoor S Boers, Clément Conil, Lucy Bizien, Justin de Brabander, Jan Willem Duitman, Alessia Romano, Jérémie Rosain, Marion Blaize, Mélanie Migaud, Maxime Jeljeli, Boualem Hammadi, Aurore Desmons, Astrid Marchal, Julien Mayaux, Qian Zhang, Emmanuelle Jouanguy, Raphael Borie, Bruno Crestani, Charles Edouard Luyt, Homa Adle-Biassette, Damien Sene, Bruno Megarbane, Aurélie Cobat, Paul Bastard, Lieuwe D J Bos, Jean-Laurent Casanova, Anne Puel

1Laboratory 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
2Imagine Institute, Université Paris Cité, Paris, EU France
3AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, EU France
4Amsterdam UMC, University of Amsterdam, Intensive Care Medicine, Meibergdreef 9, Amsterdam, EU The Netherlands
5Center for Experimental Molecular Medicine, Amsterdam UMC, Amsterdam, EU Netherlands
6Amsterdam UMC, Location AMC, Department of Pulmonary Medicine, University of Amsterdam, 1105 AZ Amsterdam, EU The Netherlands
7Amsterdam UMC, Department of Experimental Immunology, Location University of Amsterdam, 1105 AZ Amsterdam, EU The Netherlands
8Amsterdam Infection & Immunity, Inflammatory Diseases, 1105 AZ Amsterdam, EU The Netherlands
9Département 3I « Infection, Immunité Et Inflammation », Institut Cochin, INSERM U1016, Université Paris Cité, Paris, EU France
10Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d’Immunologie Biologique, Université Paris Cité, Paris, EU France
11General Chemistry Laboratory, Department of Clinical Chemistry, APHP, Necker Hospital for Sick Children, Paris, EU France
12Clinical 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
13INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, EU France
14Site Pitié-Salpêtrière, Service de Pneumologie, Médecine Intensive et Réanimation, Département R3S, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, EU France
15St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY USA
16Service de Pneumologie A Hôpital Bichat, APHP, Paris, EU France
17Inserm, PHERE, Université Paris Cité, 75018 Paris, EU France
18Service de Médecine Intensive Réanimation, Institut de Cardiologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, EU France
19Inserm, Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, EU France
20AP-HP, Hôpital Lariboisière, Service Anatomie Pathologique and Université de Paris, Paris, EU France
21Inserm, NeuroDiderot, Paris, EU France
22Internal Medicine Department, AP-HP, Lariboisière Hospital, Paris, EU France
23Université Paris Cité, Paris, EU France
24Department of Medical and Toxicological Critical Care, APHP, Lariboisière Hospital, Paris, EU France
25INSERM UMRS-1144, Paris-University, Paris, EU France
26Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France
27Department of Pediatrics, Necker Hospital for Sick Children, Paris, EU France
28Howard Hughes Medical Institute, New York, NY USA