tetano
Editor, Senior Moderator
J Clin Immunol
. 2024 Apr 22;44(4):104.
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[SUP] #[/SUP][SUP] 1 2 [/SUP], Chiaki Iwamura[SUP] #[/SUP][SUP] 1 3 [/SUP], Masahiro Kiuchi[SUP] 1 [/SUP], Kaori Tsuji[SUP] 1 [/SUP], Atsushi Sasaki[SUP] 1 [/SUP], Takahisa Hishiya[SUP] 1 [/SUP], Rui Hirasawa[SUP] 1 [/SUP], Kota Kokubo[SUP] 1 [/SUP], Sachiko Kuriyama[SUP] 1 [/SUP], Atsushi Onodera[SUP] 1 [/SUP], Tadanaga Shimada[SUP] 4 [/SUP], Tetsutaro Nagaoka[SUP] 5 [/SUP], Satoru Ishikawa[SUP] 6 [/SUP], Akira Kojima[SUP] 6 [/SUP], Haruki Mito[SUP] 7 [/SUP], Ryota Hase[SUP] 7 [/SUP], Yasunori Kasahara[SUP] 8 [/SUP], Naohide Kuriyama[SUP] 9 [/SUP], Sukeyuki Nakamura[SUP] 10 [/SUP], Takashi Urushibara[SUP] 11 [/SUP], Satoru Kaneda[SUP] 12 [/SUP], Seiichiro Sakao[SUP] 13 [/SUP], Osamu Nishida[SUP] 9 [/SUP], Kazuhisa Takahashi[SUP] 5 [/SUP], Motoko Y Kimura[SUP] 3 14 [/SUP], Shinichiro Motohashi[SUP] 15 [/SUP], Hidetoshi Igari[SUP] 16 17 [/SUP], Yuzuru Ikehara[SUP] 18 [/SUP], Hiroshi Nakajima[SUP] 3 17 19 [/SUP], Takuji Suzuki[SUP] 3 20 [/SUP], Hideki Hanaoka[SUP] 3 21 [/SUP], Taka-Aki Nakada[SUP] 4 [/SUP], Toshiaki Kikuchi[SUP] 2 [/SUP], Toshinori Nakayama[SUP] 22 23 [/SUP], Koutaro Yokote[SUP] 24 [/SUP], Kiyoshi Hirahara[SUP] 25 26 27 [/SUP]
Affiliations
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.
. 2024 Apr 22;44(4):104.
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[SUP] #[/SUP][SUP] 1 2 [/SUP], Chiaki Iwamura[SUP] #[/SUP][SUP] 1 3 [/SUP], Masahiro Kiuchi[SUP] 1 [/SUP], Kaori Tsuji[SUP] 1 [/SUP], Atsushi Sasaki[SUP] 1 [/SUP], Takahisa Hishiya[SUP] 1 [/SUP], Rui Hirasawa[SUP] 1 [/SUP], Kota Kokubo[SUP] 1 [/SUP], Sachiko Kuriyama[SUP] 1 [/SUP], Atsushi Onodera[SUP] 1 [/SUP], Tadanaga Shimada[SUP] 4 [/SUP], Tetsutaro Nagaoka[SUP] 5 [/SUP], Satoru Ishikawa[SUP] 6 [/SUP], Akira Kojima[SUP] 6 [/SUP], Haruki Mito[SUP] 7 [/SUP], Ryota Hase[SUP] 7 [/SUP], Yasunori Kasahara[SUP] 8 [/SUP], Naohide Kuriyama[SUP] 9 [/SUP], Sukeyuki Nakamura[SUP] 10 [/SUP], Takashi Urushibara[SUP] 11 [/SUP], Satoru Kaneda[SUP] 12 [/SUP], Seiichiro Sakao[SUP] 13 [/SUP], Osamu Nishida[SUP] 9 [/SUP], Kazuhisa Takahashi[SUP] 5 [/SUP], Motoko Y Kimura[SUP] 3 14 [/SUP], Shinichiro Motohashi[SUP] 15 [/SUP], Hidetoshi Igari[SUP] 16 17 [/SUP], Yuzuru Ikehara[SUP] 18 [/SUP], Hiroshi Nakajima[SUP] 3 17 19 [/SUP], Takuji Suzuki[SUP] 3 20 [/SUP], Hideki Hanaoka[SUP] 3 21 [/SUP], Taka-Aki Nakada[SUP] 4 [/SUP], Toshiaki Kikuchi[SUP] 2 [/SUP], Toshinori Nakayama[SUP] 22 23 [/SUP], Koutaro Yokote[SUP] 24 [/SUP], Kiyoshi Hirahara[SUP] 25 26 27 [/SUP]
Affiliations
- PMID: 38647550
- DOI: 10.1007/s10875-024-01708-7
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.