Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity
Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity
Summary 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.
Lehner Paul J、Wills Mark R、Lyons Paul A、Fletcher-Etherington Alice、Nightingale Katie、Bergamaschi Laura、Calero-Nieto Fernando J.、Antrobus Robin、Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration、Mescia Federica、Weekes Michael P、Smith Kenneth G.C.、Kingston Nathalie、Matheson Nicholas J、Potts Martin、Williamson James、G?ttgens Berthold、Bradley John R
Department of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeCambridge Institute for Medical Research, University of Cambridge||Department of Medicine, University of CambridgeCambridge Institute for Medical Research, University of Cambridge||Department of Medicine, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeNIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical CampusCambridge Institute for Medical Research, University of Cambridge||Department of Medicine, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeCambridge Institute for Medical Research, University of Cambridge||Department of Medicine, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeNIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus||Department of Haematology, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge||NHS Blood and TransplantCambridge Institute for Medical Research, University of Cambridge||Department of Medicine, University of CambridgeDepartment of Medicine, University of Cambridge||Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeWellcome - MRC Cambridge Stem Cell Institute, University of CambridgeDepartment of Medicine, University of Cambridge||NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus
医学研究方法基础医学细胞生物学
Lehner Paul J,Wills Mark R,Lyons Paul A,Fletcher-Etherington Alice,Nightingale Katie,Bergamaschi Laura,Calero-Nieto Fernando J.,Antrobus Robin,Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration,Mescia Federica,Weekes Michael P,Smith Kenneth G.C.,Kingston Nathalie,Matheson Nicholas J,Potts Martin,Williamson James,G?ttgens Berthold,Bradley John R.Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity[EB/OL].(2025-03-28)[2025-05-02].https://www.medrxiv.org/content/10.1101/2022.11.16.22282338.点此复制
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