Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Open Access
- 10 August 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 6 (62)
- https://doi.org/10.1126/sciimmunol.abl4340
Abstract
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.This publication has 48 references indexed in Scilit:
- Anti-Interferon Auto-Antibodies in Autoimmune Polyendocrinopathy Syndrome Type 1PLoS Medicine, 2006
- Anti-Interferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1PLoS Medicine, 2006
- Simultaneous Multiple Immunoassays in a Compact Disc–Shaped Microfluidic Device Based on Centrifugal ForceClinical Chemistry, 2005
- Characterization of the immunoreactivity of anti-interferon alpha antibodies in myasthenia gravis patients. Epitope mappingJournal of Autoimmunity, 2004
- Spontaneous production of anti-IFN- and anti-IL-12 autoantibodies by thymoma cells from myasthenia gravis patients suggests autoimmunization in the tumorInternational Immunology, 2003
- Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravisClinical and Experimental Immunology, 2003
- A solution to the problem of separation in logistic regressionStatistics in Medicine, 2002
- Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosisNeurology, 1998
- Bias reduction of maximum likelihood estimatesBiometrika, 1993
- Interferon-neutralizing antibodies in a patient treated with human fibroblast interferonNature, 1981