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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.

Titel:	Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia.
Autor/in / Beteiligte Person:	Philippot, Q ; Fekkar, A ; Gervais, A ; Le Voyer, T ; Boers, LS ; Conil, C ; Bizien, L ; de Brabander J ; Duitman, JW ; Romano, A ; Rosain, J ; Blaize, M ; Migaud, M ; Jeljeli, M ; Hammadi, B ; Desmons, A ; Marchal, A ; Mayaux, J ; Zhang, Q ; Jouanguy, E ; Borie, R ; Crestani, B ; Luyt, CE ; Adle-Biassette, H ; Sene, D ; Megarbane, B ; Cobat, A ; Bastard, P ; Bos, LDJ ; Casanova, JL ; Puel, A
Link:	View record at Springer (Volltext)
Zeitschrift:	Journal of clinical immunology, Jg. 43 (2023-08-01), Heft 6, S. 1093-1103
Veröffentlichung:	Amsterdam : Springer ; <i>Original Publication</i>: New York : Plenum, c1981-, 2023
Medientyp:	academicJournal
ISSN:	1573-2592 (electronic)
DOI:	10.1007/s10875-023-01512-9
Schlagwort:	Humans Autoantibodies Interferon-alpha Bronchoalveolar Lavage Interferon Type I COVID-19
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Corporate Authors: ArtDECO consortium ; COVID HGE consortium Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [J Clin Immunol] 2023 Aug; Vol. 43 (6), pp. 1093-1103. <i>Date of Electronic Publication: </i>2023 May 20. MeSH Terms: Interferon Type I* ; COVID-19* ; Humans ; Autoantibodies ; Interferon-alpha ; Bronchoalveolar Lavage References: Zhang Q, Bastard P, Bolze A, Jouanguy E, Zhang S-Y, COVID Human Genetic Effort, et al. Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation. Med (N Y). 2020;1:14–20. ; Zhang Q, Bastard P, COVID Human Genetic Effort, Cobat A, Casanova J-L. Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature. 2022;603:587–98. (PMID: 350901638957595) ; Brodin P. SARS-CoV-2 infections in children: Understanding diverse outcomes. Immunity. 2022;55:201–9. 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Grant Information: UL1 TR000043 United States TR NCATS NIH HHS; R01 AI088364 United States AI NIAID NIH HHS; MR/S032304/1 United Kingdom MRC_ Medical Research Council; R01 AI163029 United States AI NIAID NIH HHS; United States HHMI Howard Hughes Medical Institute; UL1 TR001866 United States TR NCATS NIH HHS Contributed Indexing: Investigator: EJ Nossent; A Saris; H De Vries; LJ Meijboom; SG Blok; AR Schuurman; TDY Reijnders; F Hugenholtz; JJG Vallejo; H Bontkes; APJ Vlaar; J Wiersinga; R Lutter; T van der Poll; HJ Bogaard; RFJ Kullberg; S Zhang; EJ Nossent; LMA Heunks; PR Tuinman; PI Bonta; L Abel; S Al-Muhsen; AA Arias; D Bogunovic; A Bolze; AA Bousfiha; D Mansouri; I Meyts; RP de Diego; V Sancho-Shimizu; AN Spaan; SG Tangye; SY Zhang; HC Su ; Keywords: COVID-19; Cytokines; SARS-CoV-2; Type I interferons Substance Nomenclature: 0 (Interferon Type I) ; 0 (Autoantibodies) ; 0 (Interferon-alpha) Entry Date(s): Date Created: 20230520 Date Completed: 20230721 Latest Revision: 20240426 Update Code: 20240426 PubMed Central ID: PMC10199445

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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.