Abstract
Original language | English |
---|---|
Pages (from-to) | 1093-1103 |
Number of pages | 11 |
Journal | Journal of clinical immunology |
Volume | 43 |
Issue number | 6 |
Early online date | 2023 |
DOIs | |
Publication status | Published - Aug 2023 |
Keywords
- COVID-19
- Cytokines
- SARS-CoV-2
- Type I interferons
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In: Journal of clinical immunology, Vol. 43, No. 6, 08.2023, p. 1093-1103.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia
AU - ArtDeco consortium
AU - Philippot, Quentin
AU - Fekkar, Arnaud
AU - Gervais, Adrian
AU - le Voyer, Tom
AU - Boers, Leonoor S.
AU - Conil, Clément
AU - Bizien, Lucy
AU - de Brabander, Justin
AU - Duitman, Jan Willem
AU - Romano, Alessia
AU - Rosain, J. rémie
AU - Blaize, Marion
AU - Migaud, M. lanie
AU - Jeljeli, Maxime
AU - Hammadi, Boualem
AU - Desmons, Aurore
AU - Marchal, Astrid
AU - Nossent, Esther J.
AU - COVID HGE consortium
AU - Saris, Anno
AU - de Vries, Heder
AU - Meijboom, Lilian J.
AU - Blok, Siebe G.
AU - Schuurman, Alex R.
AU - Reijnders, Tom D. Y.
AU - Hugenholtz, F.
AU - Vallejo, Juan J. Garcia
AU - Bontkes, Hetty
AU - Vlaar, Alexander P. J.
AU - Wiersinga, Joost
AU - Lutter, René
AU - van der Poll, Tom
AU - Bogaard, Harm Jan
AU - Kullberg, Robert F. J.
AU - Zhang, Shiqi
AU - Nossent, Esther J.
AU - Heunks, Leo M. A.
AU - Tuinman, Pieter Roel
AU - Bonta, Peter I.
AU - Abel, Laurent
AU - Al-Muhsen, Saleh
AU - Arias, Andrés A.
AU - Bogunovic, Dusan
AU - Bolze, Alexandre
AU - Bousfiha, Ahmed A.
AU - Mansouri, Davood
AU - Meyts, Isabelle
AU - de Diego, Rebeca Perez
AU - Sancho-Shimizu, Vanessa
AU - Spaan, András N.
AU - Bos, Lieuwe D. J.
N1 - Funding Information: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), ANR AI2D (ANR-22-CE15-0046), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU COVIFERON Program (ANR-21-RHUS-08), the Square Foundation, Grandir—Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM and Paris Cité University. Q.P was supported by the Assistance Publique-Hôpitaux de Paris (Année Recherche) and by the MD-PhD program of INSERM (Ecole de l’INSERM Liliane Bettencourt). J.R., T.L.V. and P.B. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). J.R. was supported by the Inserm PhD program (“poste d’accueil Inserm”). P.B. was supported by the FRM (EA20170638020). L.D.J.B is supported by Amsterdam UMC through the fellowship program, by the Innovative Health Institute, by Longfonds (the Dutch Lung Foundation; Dirkje Postma Award), by the European Respiratory Society (ARDS gold medal) and by the Amsterdam UMC fellowship and ZonMW through the COVID-19 urgent grant. Funding Information: We thank the patients for placing their trust in us. We thank the members of both branches of the Laboratory of Human Genetics of Infectious Diseases. We thank Yelena Nemirovskaya, Mark Woollett, Dana Liu, Soraya Boucherit, Erin Williams, Christine Rivalain, Maya Chrabieh, and Lazaro Lorenzo for administrative assistance. ArtDECO consortium Esther J. Nossent1, Anno Saris1, Heder De Vries1, Lilian J. Meijboom1, Siebe G. Blok1, Alex R. Schuurman1, Tom D.Y. Reijnders1, F. Hugenholtz1, Juan J. Garcia Vallejo1, Hetty Bontkes1, Alexander P.J. Vlaar1, Joost Wiersinga1, René Lutter1, Tom van der Poll1, Harm Jan Bogaard1, Robert F.J. Kullberg1, Shiqi Zhang, Esther J. Nossent1, Leo M.A. Heunks1, Pieter Roel Tuinman1, Peter I. Bonta1.1Amsterdam University Medical Centers, Amsterdam, the Netherlands, EU. Consortium representative: Lieuwe D.J. Bos—l.d.bos@amsterdamumc.nl COVID HGE consortium Laurent Abel1, Saleh Al-Muhsen2, Andrés A. Arias3,4, Dusan Bogunovic5, Alexandre Bolze6, Ahmed A. Bousfiha7, Davood Mansouri8, Isabelle Meyts9, Rebeca Perez de Diego10, Vanessa Sancho-Shimizu11, András N. Spaan3,12, Stuart G. Tangye13, Shen-Ying Zhang3, Helen C. Su14.1Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France.2Immunology Research Laboratory, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.3St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.4Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia, Medellín, Colombia; School of Microbiology, University of Antioquia UdeA, Medellín, Colombia.5Icahn School of Medicine at Mount Sinai, New York, NY, USA.6Helix, San Mateo, CA, USA.7Department of Pediatric Infectious Diseases and Clinical Immunology, CHU; Ibn Rushd and LICIA, Laboratoire d'Immunologie Clinique, Inflammation et Allergie, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.8Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, The Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti, University of Medical Sciences, Tehran, Iran.9Department of Pediatrics, University Hospitals Leuven; KU Leuven, Department of Microbiology, Immunology and Transplantation; Laboratory for Inborn Errors of Immunity, KU Leuven, Leuven, Belgium.10Institute of Biomedical Research of IdiPAZ, University Hospital “La Paz”, Madrid, Spain.11Department of Pediatric Infectious Diseases and Virology, Imperial College London, London, UK; Centre for Pediatrics and Child Health, Faculty of Medicine, Imperial College London, London, UK.12Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands.13Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.14National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Consortium representative: Jean-Laurent Casanova—casanova@mail.rockefeller.edu Publisher Copyright: © 2023, The Author(s).
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - COVID-19
KW - Cytokines
KW - SARS-CoV-2
KW - Type I interferons
UR - http://www.scopus.com/inward/record.url?scp=85160413818&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s10875-023-01512-9
DO - https://doi.org/10.1007/s10875-023-01512-9
M3 - Article
C2 - 37209324
SN - 0271-9142
VL - 43
SP - 1093
EP - 1103
JO - Journal of clinical immunology
JF - Journal of clinical immunology
IS - 6
ER -