1. Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.
- Author
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Aoki A, Iwamura C, Kiuchi M, Tsuji K, Sasaki A, Hishiya T, Hirasawa R, Kokubo K, Kuriyama S, Onodera A, Shimada T, Nagaoka T, Ishikawa S, Kojima A, Mito H, Hase R, Kasahara Y, Kuriyama N, Nakamura S, Urushibara T, Kaneda S, Sakao S, Nishida O, Takahashi K, Kimura MY, Motohashi S, Igari H, Ikehara Y, Nakajima H, Suzuki T, Hanaoka H, Nakada TA, Kikuchi T, Nakayama T, Yokote K, and Hirahara K
- Subjects
- Female, Humans, Male, Dendritic Cells immunology, SARS-CoV-2 immunology, Severity of Illness Index, Signal Transduction immunology, Autoantibodies immunology, Autoantibodies blood, COVID-19 immunology, Interferon Type I immunology, Interferon Type I metabolism, Myeloid Cells immunology
- Abstract
Purpose: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs., Methods: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs., Results: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor., Conclusion: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity., (© 2024. The Author(s).)
- Published
- 2024
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