tetano
Editor, Senior Moderator
Cell Rep
. 2023 May 29;42(6):112613.
doi: 10.1016/j.celrep.2023.112613. Online ahead of print. Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity
Martin Potts[SUP] 1 [/SUP], Alice Fletcher-Etherington[SUP] 1 [/SUP], Katie Nightingale[SUP] 1 [/SUP], Federica Mescia[SUP] 2 [/SUP], Laura Bergamaschi[SUP] 2 [/SUP], Fernando J Calero-Nieto[SUP] 3 [/SUP], Robin Antrobus[SUP] 1 [/SUP], James Williamson[SUP] 2 [/SUP]; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Harriet Parsons[SUP] 1 [/SUP], Edward L Huttlin[SUP] 3 [/SUP], Nathalie Kingston[SUP] 4 [/SUP], Berthold Göttgens[SUP] 5 [/SUP], John R Bradley[SUP] 6 [/SUP], Paul J Lehner[SUP] 2 [/SUP], Nicholas J Matheson[SUP] 7 [/SUP], Kenneth G C Smith[SUP] 2 [/SUP], Mark R Wills[SUP] 2 [/SUP], Paul A Lyons[SUP] 2 [/SUP], Michael P Weekes[SUP] 8 [/SUP]
Affiliations
Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. 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[SUP]+[/SUP]CD4[SUP]+[/SUP]CEACAM1/6/8[SUP]+[/SUP]CD177[SUP]+[/SUP]CD63[SUP]+[/SUP]CD89[SUP]+[/SUP] and CD16[SUP]+[/SUP]CEACAM1/6/8[SUP]+[/SUP] mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology.
. 2023 May 29;42(6):112613.
doi: 10.1016/j.celrep.2023.112613. Online ahead of print. Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity
Martin Potts[SUP] 1 [/SUP], Alice Fletcher-Etherington[SUP] 1 [/SUP], Katie Nightingale[SUP] 1 [/SUP], Federica Mescia[SUP] 2 [/SUP], Laura Bergamaschi[SUP] 2 [/SUP], Fernando J Calero-Nieto[SUP] 3 [/SUP], Robin Antrobus[SUP] 1 [/SUP], James Williamson[SUP] 2 [/SUP]; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Harriet Parsons[SUP] 1 [/SUP], Edward L Huttlin[SUP] 3 [/SUP], Nathalie Kingston[SUP] 4 [/SUP], Berthold Göttgens[SUP] 5 [/SUP], John R Bradley[SUP] 6 [/SUP], Paul J Lehner[SUP] 2 [/SUP], Nicholas J Matheson[SUP] 7 [/SUP], Kenneth G C Smith[SUP] 2 [/SUP], Mark R Wills[SUP] 2 [/SUP], Paul A Lyons[SUP] 2 [/SUP], Michael P Weekes[SUP] 8 [/SUP]
Affiliations
- PMID: 37302069
- DOI: 10.1016/j.celrep.2023.112613
Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. 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[SUP]+[/SUP]CD4[SUP]+[/SUP]CEACAM1/6/8[SUP]+[/SUP]CD177[SUP]+[/SUP]CD63[SUP]+[/SUP]CD89[SUP]+[/SUP] and CD16[SUP]+[/SUP]CEACAM1/6/8[SUP]+[/SUP] mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology.