Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients

Ami Aoki; Chiaki Iwamura; Masahiro Kiuchi; Kaori Tsuji; Atsushi Sasaki; Takahisa Hishiya; Rui Hirasawa; Kota Kokubo; Sachiko Kuriyama; Atsushi Onodera; Tadanaga Shimada; Tetsutaro Nagaoka; Satoru Ishikawa; Akira Kojima; Haruki Mito; Ryota Hase; Yasunori Kasahara; Naohide Kuriyama; Sukeyuki Nakamura; Takashi Urushibara; Satoru Kaneda; Seiichiro Sakao; Osamu Nishida; Kazuhisa Takahashi; Motoko Y. Kimura; Shinichiro Motohashi; Hidetoshi Igari; Yuzuru Ikehara; Hiroshi Nakajima; Takuji Suzuki; Hideki Hanaoka; Taka Aki Nakada; Toshiaki Kikuchi; Toshinori Nakayama; Koutaro Yokote; Kiyoshi Hirahara

doi:10.1007/s10875-024-01708-7

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients

Ami Aoki, Chiaki Iwamura, Masahiro Kiuchi, Kaori Tsuji, Atsushi Sasaki, Takahisa Hishiya, Rui Hirasawa, Kota Kokubo, Sachiko Kuriyama, Atsushi Onodera, Tadanaga Shimada, Tetsutaro Nagaoka, Satoru Ishikawa, Akira Kojima, Haruki Mito, Ryota Hase, Yasunori Kasahara, Naohide Kuriyama, Sukeyuki Nakamura, Takashi UrushibaraSatoru Kaneda, Seiichiro Sakao, Osamu Nishida, Kazuhisa Takahashi, Motoko Y. Kimura, Shinichiro Motohashi, Hidetoshi Igari, Yuzuru Ikehara, Hiroshi Nakajima, Takuji Suzuki, Hideki Hanaoka, Taka Aki Nakada, Toshiaki Kikuchi, Toshinori Nakayama, Koutaro Yokote, Kiyoshi Hirahara

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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.

Original language	English
Article number	104
Journal	Journal of Clinical Immunology
Volume	44
Issue number	4
DOIs	https://doi.org/10.1007/s10875-024-01708-7
Publication status	Published - 04-2024
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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10.1007/s10875-024-01708-7

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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., ... Hirahara, K. (2024). Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients. Journal of Clinical Immunology, 44(4), Article 104. https://doi.org/10.1007/s10875-024-01708-7

@article{c2b31d4cd3d7405b911a3f99933ad845,

title = "Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients",

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.",

keywords = "Autoantibody, BCR repertoires, COVID-19, Epitope mapping, Single-cell RNA sequencing, Type I IFNs",

author = "Ami Aoki and Chiaki Iwamura and Masahiro Kiuchi and Kaori Tsuji and Atsushi Sasaki and Takahisa Hishiya and Rui Hirasawa and Kota Kokubo and Sachiko Kuriyama and Atsushi Onodera and Tadanaga Shimada and Tetsutaro Nagaoka and Satoru Ishikawa and Akira Kojima and Haruki Mito and Ryota Hase and Yasunori Kasahara and Naohide Kuriyama and Sukeyuki Nakamura and Takashi Urushibara and Satoru Kaneda and Seiichiro Sakao and Osamu Nishida and Kazuhisa Takahashi and Kimura, {Motoko Y.} and Shinichiro Motohashi and Hidetoshi Igari and Yuzuru Ikehara and Hiroshi Nakajima and Takuji Suzuki and Hideki Hanaoka and Nakada, {Taka Aki} and Toshiaki Kikuchi and Toshinori Nakayama and Koutaro Yokote and Kiyoshi Hirahara",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = apr,

doi = "10.1007/s10875-024-01708-7",

language = "English",

volume = "44",

journal = "Journal of Clinical Immunology",

issn = "0271-9142",

publisher = "Springer",

number = "4",

}

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 & Hirahara, K 2024, 'Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients', Journal of Clinical Immunology, vol. 44, no. 4, 104. https://doi.org/10.1007/s10875-024-01708-7

TY - JOUR

T1 - Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients

AU - Aoki, Ami

AU - Iwamura, Chiaki

AU - Kiuchi, Masahiro

AU - Tsuji, Kaori

AU - Sasaki, Atsushi

AU - Hishiya, Takahisa

AU - Hirasawa, Rui

AU - Kokubo, Kota

AU - Kuriyama, Sachiko

AU - Onodera, Atsushi

AU - Shimada, Tadanaga

AU - Nagaoka, Tetsutaro

AU - Ishikawa, Satoru

AU - Kojima, Akira

AU - Mito, Haruki

AU - Hase, Ryota

AU - Kasahara, Yasunori

AU - Kuriyama, Naohide

AU - Nakamura, Sukeyuki

AU - Urushibara, Takashi

AU - Kaneda, Satoru

AU - Sakao, Seiichiro

AU - Nishida, Osamu

AU - Takahashi, Kazuhisa

AU - Kimura, Motoko Y.

AU - Motohashi, Shinichiro

AU - Igari, Hidetoshi

AU - Ikehara, Yuzuru

AU - Nakajima, Hiroshi

AU - Suzuki, Takuji

AU - Hanaoka, Hideki

AU - Nakada, Taka Aki

AU - Kikuchi, Toshiaki

AU - Nakayama, Toshinori

AU - Yokote, Koutaro

AU - Hirahara, Kiyoshi

PY - 2024/4

Y1 - 2024/4

N2 - 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.

AB - 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.

KW - Autoantibody

KW - BCR repertoires

KW - COVID-19

KW - Epitope mapping

KW - Single-cell RNA sequencing

KW - Type I IFNs

UR - http://www.scopus.com/inward/record.url?scp=85190844584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85190844584&partnerID=8YFLogxK

U2 - 10.1007/s10875-024-01708-7

DO - 10.1007/s10875-024-01708-7

M3 - Article

C2 - 38647550

AN - SCOPUS:85190844584

SN - 0271-9142

VL - 44

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

IS - 4

M1 - 104

ER -

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients

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