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

J Exp Med. 2021 Jul 5;218(7):e20210554. doi: 10.1084/jem.20210554.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / immunology*
  • COVID-19 / immunology*
  • Child
  • Female
  • Humans
  • Interferon Type I / immunology*
  • Male
  • Middle Aged
  • Pneumonia / immunology*
  • Polyendocrinopathies, Autoimmune / immunology*
  • SARS-CoV-2 / immunology
  • Young Adult

Substances

  • Autoantibodies
  • Interferon Type I
  • interferon kappa

Supplementary concepts

  • Autoimmune polyendocrinopathy syndrome, type 1