Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients

Helen Ashwin; Luke Milross; Julie Wilson; Joaquim Majo; Jimmy Tsz Hang Lee; Grant Calder; Bethany Hunter; Sally James; Dimitris Lagos; Nathalie Signoret; Andrew Filby; Omer Ali Bayraktar; Andrew J Fisher; Paul M Kaye

doi:10.1136/jcp-2023-208771

Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients

Helen Ashwin, Luke Milross, Julie Wilson, Joaquim Majo, Jimmy Tsz Hang Lee, Grant Calder, Bethany Hunter, Sally James, Dimitris Lagos, Nathalie Signoret, Andrew Filby, Omer Ali Bayraktar, Andrew J Fisher, Paul M Kaye

Research output: Contribution to journal › Article › peer-review

Abstract

Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage. Here, we applied highly multiplexed spatial protein profiling to autopsy lung tissues derived from 27 patients who died from COVID-19 and identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246) and VISTA) that distinguishes early DAD from late DAD with good predictive accuracy. These proteins warrant further investigation as potential regulators of DAD progression.

Original language	English
Number of pages	5
Journal	Journal of clinical pathology
Early online date	9 Mar 2023
DOIs	https://doi.org/10.1136/jcp-2023-208771
Publication status	E-pub ahead of print - 9 Mar 2023

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Ashwin, H., Milross, L., Wilson, J., Majo, J., Hang Lee, J. T., Calder, G., Hunter, B., James, S., Lagos, D., Signoret, N., Filby, A., Bayraktar, O. A., Fisher, A. J., & Kaye, P. M. (2023). Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients. Journal of clinical pathology. Advance online publication. https://doi.org/10.1136/jcp-2023-208771

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title = "Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients",

abstract = "Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage. Here, we applied highly multiplexed spatial protein profiling to autopsy lung tissues derived from 27 patients who died from COVID-19 and identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246) and VISTA) that distinguishes early DAD from late DAD with good predictive accuracy. These proteins warrant further investigation as potential regulators of DAD progression.",

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AU - Ashwin, Helen

AU - Milross, Luke

AU - Wilson, Julie

AU - Majo, Joaquim

AU - Hang Lee, Jimmy Tsz

AU - Calder, Grant

AU - Hunter, Bethany

AU - James, Sally

AU - Lagos, Dimitris

AU - Signoret, Nathalie

AU - Filby, Andrew

AU - Bayraktar, Omer Ali

AU - Fisher, Andrew J

AU - Kaye, Paul M

PY - 2023/3/9

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N2 - Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage. Here, we applied highly multiplexed spatial protein profiling to autopsy lung tissues derived from 27 patients who died from COVID-19 and identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246) and VISTA) that distinguishes early DAD from late DAD with good predictive accuracy. These proteins warrant further investigation as potential regulators of DAD progression.

AB - Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage. Here, we applied highly multiplexed spatial protein profiling to autopsy lung tissues derived from 27 patients who died from COVID-19 and identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246) and VISTA) that distinguishes early DAD from late DAD with good predictive accuracy. These proteins warrant further investigation as potential regulators of DAD progression.

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