Autoantibodies targeting type I interferons: Prevalence, mechanisms of induction, and association with viral disease susceptibility.
Eur J Immunol
; 53(6): e2250164, 2023 06.
Article
in English
| MEDLINE | ID: covidwho-2296074
ABSTRACT
The type I IFN (IFN-I) system is essential to limit severe viral disease in humans. Thus, IFN-I deficiencies are associated with serious life-threatening infections. Remarkably, some rare individuals with chronic autoimmune diseases develop neutralizing autoantibodies (autoAbs) against IFN-Is thereby compromising their own innate antiviral defenses. Furthermore, the prevalence of anti-IFN-I autoAbs in apparently healthy individuals increases with age, such that â¼4% of those over 70 years old are affected. Here, I review the literature on factors that may predispose individuals to develop anti-IFN-I autoAbs, such as reduced self-tolerance caused by defects in the genes AIRE, NFKB2, and FOXP3 (among others), or by generally impaired thymus function, including thymic involution in the elderly. In addition, I discuss the hypothesis that predisposed individuals develop anti-IFN-I autoAbs following "autoimmunization" with IFN-Is generated during some acute viral infections, systemic inflammatory events, or chronic IFN-I exposure. Finally, I highlight the enhanced susceptibility that individuals with anti-IFN-I autoAbs appear to have towards viral diseases such as severe COVID-19, influenza, or herpes (e.g., varicella-zoster virus, herpes simplex virus, cytomegalovirus), as well as adverse reactions to live-attenuated vaccines. Understanding the mechanisms underlying development and consequences of anti-IFN-I autoAbs will be key to implementing effective prophylactic and therapeutic measures.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
Interferon Type I
/
COVID-19
Type of study:
Observational study
Topics:
Vaccines
Limits:
Aged
/
Humans
Language:
English
Journal:
Eur J Immunol
Year:
2023
Document Type:
Article
Affiliation country:
Eji.202250164
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