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Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity
Martin Potts; Alice Fletcher-Etherington; Katie Nightingale; Federica Mescia; Laura Bergamaschi; Fernando J Calero-Nieto; Robin Antrobus; James Williamson; - CITIID-NIHR COVID BioResource Collaboration; Nathalie Kingston; Berthold Gottgens; John R Bradley; Paul J Lehner; Nicholas J Matheson; Kenneth GC Smith; Mark R Wills; Paul A Lyons; Michael P Weekes.
Afiliación
  • Martin Potts; Cambridge Institute for Medical Research, University of Cambridge; Department of Medicine, University of Cambridge
  • Alice Fletcher-Etherington; Cambridge Institute for Medical Research, University of Cambridge; Department of Medicine, University of Cambridge
  • Katie Nightingale; Cambridge Institute for Medical Research, University of Cambridge; Department of Medicine, University of Cambridge
  • Federica Mescia; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Laura Bergamaschi; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Fernando J Calero-Nieto; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Robin Antrobus; Cambridge Institute for Medical Research, University of Cambridge; Department of Medicine, University of Cambridge
  • James Williamson; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • - CITIID-NIHR COVID BioResource Collaboration;
  • Nathalie Kingston; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge; Department of Haematology, University of Cambridge
  • Berthold Gottgens; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge
  • John R Bradley; Department of Medicine, University of Cambridge; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge
  • Paul J Lehner; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Nicholas J Matheson; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Kenneth GC Smith; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Mark R Wills; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Paul A Lyons; Department of Medicine, University of Cambridge; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Universi
  • Michael P Weekes; Cambridge Institute for Medical Research, University of Cambridge; Department of Medicine, University of Cambridge
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22282338
ABSTRACT
Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CD177+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Cohort_studies / Observational_studies / Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Cohort_studies / Observational_studies / Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Preprint