Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann H, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J, Shaw E, Haljasmägi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodríguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J, HGID Lab , NIAID-USUHS Immune Response to COVID Group , COVID Clinicians , COVID-STORM Clinicians , Imagine COVID Group , French COVID Cohort Study Group , Milieu Intérieur Consortium , CoV-Contact Cohort , Amsterdam UMC Covid-19 Biobank , COVID Human Genetic Effort , Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang S, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, Casanova J

Science 370 (6515) - [2020-10-23; online 2020-09-24]

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Category: Genomics & transcriptomics

Type: Journal article

PubMed 32972996

DOI 10.1126/science.abd4585

Crossref 10.1126/science.abd4585

Supplementary materials include: clinical, epidemiological characteristics of 101 patients, as well as information on neutralising capacity and assays
NA: Plasma, cells, and genomic DNA are available under a material agreement.


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