Detection of in vivo inflammasome activation for predicting sepsis mortality
Sepsis is a severe life-threatening syndrome caused by dysregulated host responses to infection. Biomarkers that allow for monitoring the patient’s immune status are needed. Recently, a flow cytometry-based detection of in vivo inflammasome activation by formation of cytoplasmic aggregates of ASC (a...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
04 February 2021
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| In: |
Frontiers in immunology
Year: 2021, Volume: 11, Pages: 1-11 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.613745 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2020.613745 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2020.613745/full 
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| Author Notes: | Jing Cui, Stephanie Oehrl, Fareed Ahmad, Thorsten Brenner, Florian Uhle, Christian Nusshag, Christoph Rupp, Felix Funck, Stefan Meisel, Markus A. Weigand, Christian Morath and Knut Schäkel |
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| 520 | |a Sepsis is a severe life-threatening syndrome caused by dysregulated host responses to infection. Biomarkers that allow for monitoring the patient’s immune status are needed. Recently, a flow cytometry-based detection of in vivo inflammasome activation by formation of cytoplasmic aggregates of ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) has been proposed. Here we report on the frequency of ASC-speck+ leukocytes correlating with the survival of sepsis. 25 patients with sepsis were sampled consecutively for 7 days. Blood, serum samples and patient data were collected according to the guidelines of the PredARRT-Sep-Trial. Flow cytometric analysis was performed on fresh whole blood samples to investigate the formation of ASC-specks in leukocyte subsets. Serum samples were analyzed for production of IL-1ß, IL-18 and additional inflammatory markers. ASC-speck formation was found to be increased in leukocytes from sepsis patients compared to healthy donor controls. The absolute number of ASC-speck+ neutrophils peaked on day 1. For monocytes, the highest percentage and maximum absolute number of ASC-speck+ cells were detected on day 6 and day 7. Inflammatory cytokines were elevated on day 1 and declined thereafter, with exception of IL-18. Survival analysis showed that patients with lower absolute numbers of ASC-speck+ monocytes (<1650 cells/ml) on day 6 had a lower probability to survive, with an hazard ratio (HR) of 10.178. Thus, the frequency of ASC-speck+ monocytes on day 6 after onset of sepsis may serve to identify patients at risk of death from sepsis. | ||
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