Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.
Autoantibody
BCR repertoires
COVID-19
Epitope mapping
Single-cell RNA sequencing
Type I IFNs
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
22 Apr 2024
22 Apr 2024
Historique:
received:
07
06
2023
accepted:
10
04
2024
medline:
22
4
2024
pubmed:
22
4
2024
entrez:
22
4
2024
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 38647550
doi: 10.1007/s10875-024-01708-7
pii: 10.1007/s10875-024-01708-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) Grants-in-Aid for Scientific Research
ID : (S) 26221305
Organisme : Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) Grants-in-Aid for Scientific Research
ID : (B) 20H03685
Organisme : Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) Grants-in-Aid for Scientific Research
ID : (C) 17K08876
Organisme : Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) Grants-in-Aid for Scientific Research
ID : (C) 18K07164
Organisme : Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) Grants-in-Aid for Scientific Research
ID : 19K16683
Organisme : Transformative Research Areas
ID : (B) JP21H05120
Organisme : Transformative Research Areas
ID : (B) JP21H05121
Organisme : Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development, AMED
ID : JP21ek0410060
Organisme : Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development, AMED
ID : JP21ek0410082
Organisme : Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development, AMED
ID : JP19ek0410045
Organisme : AMED-PRIME
ID : JP20gm6110005
Organisme : AMED-CREST
ID : JP21gm1210003
Organisme : JST FOREST Project
ID : JPMJFR200R
Informations de copyright
© 2024. The Author(s).
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