Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1-Reference-Cited by-同舟云学术

Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

Published:2021-04-23 Issue:7 Volume:218 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Bastard Paul¹²³^ORCID,Orlova Elizaveta⁴^ORCID,Sozaeva Leila⁴^ORCID,Lévy Romain¹²⁵^ORCID,James Alyssa⁶^ORCID,Schmitt Monica M.⁶^ORCID,Ochoa Sebastian⁶^ORCID,Kareva Maria⁴^ORCID,Rodina Yulia⁷^ORCID,Gervais Adrian¹²^ORCID,Le Voyer Tom¹²^ORCID,Rosain Jérémie¹²^ORCID,Philippot Quentin¹²^ORCID,Neehus Anna-Lena¹²^ORCID,Shaw Elana⁶^ORCID,Migaud Mélanie¹^ORCID,Bizien Lucy¹^ORCID,Ekwall Olov⁸⁹^ORCID,Berg Stefan⁸^ORCID,Beccuti Guglielmo¹⁰^ORCID,Ghizzoni Lucia¹⁰^ORCID,Thiriez Gérard¹¹^ORCID,Pavot Arthur¹²^ORCID,Goujard Cécile¹³^ORCID,Frémond Marie-Louise⁵¹⁴^ORCID,Carter Edwin¹⁵^ORCID,Rothenbuhler Anya¹⁶^ORCID,Linglart Agnès¹⁶^ORCID,Mignot Brigite¹⁷^ORCID,Comte Aurélie¹⁷^ORCID,Cheikh Nathalie¹⁸^ORCID,Hermine Olivier²¹⁹^ORCID,Breivik Lars²⁰^ORCID,Husebye Eystein S.²⁰²¹²²^ORCID,Humbert Sébastien²³^ORCID,Rohrlich Pierre²⁴^ORCID,Coaquette Alain²⁵^ORCID,Vuoto Fanny²⁶^ORCID,Faure Karine²⁶^ORCID,Mahlaoui Nizar⁵²⁷^ORCID,Kotnik Primož²⁸²⁹^ORCID,Battelino Tadej²⁸²⁹^ORCID,Trebušak Podkrajšek Katarina²⁸²⁹^ORCID,Kisand Kai³⁰^ORCID,Ferré Elise M.N.⁶^ORCID,DiMaggio Thomas⁶^ORCID,Rosen Lindsey B.⁶^ORCID,Burbelo Peter D.³¹^ORCID,McIntyre Martin³²^ORCID,Kann Nelli Y.⁷^ORCID,Shcherbina Anna⁷^ORCID,Pavlova Maria³³^ORCID,Kolodkina Anna⁴^ORCID,Holland Steven M.⁶^ORCID,Zhang Shen-Ying¹²³^ORCID,Crow Yanick J.¹⁴¹⁵^ORCID,Notarangelo Luigi D.⁶^ORCID,Su Helen C.⁶^ORCID,Abel Laurent¹²³^ORCID,Anderson Mark S.³⁴^ORCID,Jouanguy Emmanuelle¹²³^ORCID,Neven Bénédicte²⁵^ORCID,Puel Anne¹²³^ORCID,Casanova Jean-Laurent¹²³³⁵^ORCID,Lionakis Michail S.⁶^ORCID

Affiliation:

1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France

2. University of Paris, Imagine Institute, Paris, France

3. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY

4. Endocrinology Research Centre, Moscow, Russia

5. Pediatric Immunology, Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris, Paris, France

6. Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

7. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia

8. Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden

9. Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden

10. Department of Medical Sciences, University of Turin, Turin, Italy

11. Intensive Care Unit, Besançon Hospital, Besançon, France

12. Intensive Care Unit, Kremlin-Bicêtre Hospital, Kremlin-Bicêtre, France

13. Internal Medicine Department, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris, Paris Saclay University, Institut National de la Santé et de la Recherche Médicale U1018, Le Kremlin-Bicêtre, France

14. Laboratory of Neurogenetics and Neuroinflammation, Université de Paris, Imagine Institute, Paris, France

15. Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, Edinburgh, UK

16. Pediatric Endocrinology Department, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris, Paris Saclay University, Le Kremlin-Bicêtre, France

17. Pediatric Medicine Unit, University Hospital of Besançon, Besançon, France

18. Pediatric Hematology Unit, University Hospital of Besançon, Besançon, France

19. Hematology department, University of Paris, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris, Paris, France

20. Department of Clinical Science and K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway

21. Department of Medicine, Haukeland University Hospital, Bergen, Norway

22. Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

23. Internal Medicine Unit, Besançon Hospital, Besançon, France

24. Pediatric Hematology and Oncology unit, Centre Hospitalier Universitaire de Nice, Nice, France

25. Laboratory of Virology, Besançon Hospital, Besançon, France

26. Infectious Disease Unit, Lille Hospital, Lille, France

27. Centre de Référence Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France

28. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

29. University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, Slovenia

30. Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia

31. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD

32. Royal Alexandra Hospital, Paisley, Scotland, UK

33. Department of Endocrinology N°1, Sechenov University, Moscow, Russia

34. Diabetes Center, University of California, San Francisco, San Francisco, CA

35. Howard Hughes Medical Institute, New York, NY

Abstract

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

Funder

Howard Hughes Medical Institute

The Rockefeller University

St. Giles Foundation

NIH

National Center for Advancing Translational Sciences

Emergent Ventures

George Mason University

National Human Genome Research Institute

Yale High Performance Computing Center

Fisher Center for Alzheimer’s Research Foundation

Meyer Foundation