Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1.
J Clin Invest
; 131(14)2021 07 15.
Article
in English
| MEDLINE | ID: covidwho-1311204
ABSTRACT
Autoantibodies against IFN-α and IFN-ω (type I IFNs) were recently reported as causative for severe COVID-19 in the general population. Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. We therefore hypothesized that autoantibodies against type I IFNs also predispose patients with APS-1 to severe COVID-19. We prospectively studied 6 patients with APS-1 between April 1, 2020 and April 1, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies against IFN-α and IFN-ω. The ability of the patients' sera to block recombinant human IFN-α and IFN-ω was assessed by assays quantifying phosphorylation of signal transducer and activator of transcription 1 (STAT1) as well as infection-based IFN-neutralization assays. We describe 4 patients with APS-1 and preexisting high titers of neutralizing autoantibodies against IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnea, oxygen requirement, or high temperature. All infected patients with APS-1 were females and younger than 26 years of age. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Autoantibodies
/
Interferon Type I
/
Polyendocrinopathies, Autoimmune
/
SARS-CoV-2
/
COVID-19
Type of study:
Case report
/
Prognostic study
Topics:
Long Covid
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Young adult
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
JCI150867
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