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Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis
Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulati...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019484/ https://www.ncbi.nlm.nih.gov/pubmed/31906585 http://dx.doi.org/10.3390/jcm9010127 |
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author | Liepelt, Anke Hohlstein, Philipp Gussen, Hendrik Xue, Jia Aschenbrenner, Anna C. Ulas, Thomas Buendgens, Lukas Warzecha, Klaudia T. Bartneck, Matthias Luedde, Tom Trautwein, Christian Schultze, Joachim L. Koch, Alexander Tacke, Frank |
author_facet | Liepelt, Anke Hohlstein, Philipp Gussen, Hendrik Xue, Jia Aschenbrenner, Anna C. Ulas, Thomas Buendgens, Lukas Warzecha, Klaudia T. Bartneck, Matthias Luedde, Tom Trautwein, Christian Schultze, Joachim L. Koch, Alexander Tacke, Frank |
author_sort | Liepelt, Anke |
collection | PubMed |
description | Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulating CD14(+) monocytes from healthy volunteers (n = 54) and intensive care unit (ICU) patients (n = 76), of which n = 36 had sepsis. RNA sequencing of selected samples revealed that monocytes from septic ICU patients display a peculiar activation pattern, which resembles characteristic functional stages of monocyte-derived macrophages and is distinct from controls or non-sepsis ICU patients. Focusing on 55 highly variable genes selected for further investigation, arachidonate 5-lipoxygenase-activating protein (ALOX5AP) was highly upregulated in monocytes of ICU patients and only normalized during 7 days in the ICU in non-sepsis patients. Strikingly, low monocytic guanine nucleotide exchange factor 10-like protein (ARHGEF10L) mRNA expression was associated with the disease severity and mortality of ICU patients. Collectively, our comprehensive analysis of circulating monocytes in critically ill patients revealed a distinct activation pattern, particularly in ICU patients with sepsis. The association with disease severity, the longitudinal recovery or lack thereof during the ICU stay, and the association with prognosis indicate the clinical relevance of monocytic gene expression profiles during sepsis. |
format | Online Article Text |
id | pubmed-7019484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70194842020-03-09 Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis Liepelt, Anke Hohlstein, Philipp Gussen, Hendrik Xue, Jia Aschenbrenner, Anna C. Ulas, Thomas Buendgens, Lukas Warzecha, Klaudia T. Bartneck, Matthias Luedde, Tom Trautwein, Christian Schultze, Joachim L. Koch, Alexander Tacke, Frank J Clin Med Article Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulating CD14(+) monocytes from healthy volunteers (n = 54) and intensive care unit (ICU) patients (n = 76), of which n = 36 had sepsis. RNA sequencing of selected samples revealed that monocytes from septic ICU patients display a peculiar activation pattern, which resembles characteristic functional stages of monocyte-derived macrophages and is distinct from controls or non-sepsis ICU patients. Focusing on 55 highly variable genes selected for further investigation, arachidonate 5-lipoxygenase-activating protein (ALOX5AP) was highly upregulated in monocytes of ICU patients and only normalized during 7 days in the ICU in non-sepsis patients. Strikingly, low monocytic guanine nucleotide exchange factor 10-like protein (ARHGEF10L) mRNA expression was associated with the disease severity and mortality of ICU patients. Collectively, our comprehensive analysis of circulating monocytes in critically ill patients revealed a distinct activation pattern, particularly in ICU patients with sepsis. The association with disease severity, the longitudinal recovery or lack thereof during the ICU stay, and the association with prognosis indicate the clinical relevance of monocytic gene expression profiles during sepsis. MDPI 2020-01-02 /pmc/articles/PMC7019484/ /pubmed/31906585 http://dx.doi.org/10.3390/jcm9010127 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liepelt, Anke Hohlstein, Philipp Gussen, Hendrik Xue, Jia Aschenbrenner, Anna C. Ulas, Thomas Buendgens, Lukas Warzecha, Klaudia T. Bartneck, Matthias Luedde, Tom Trautwein, Christian Schultze, Joachim L. Koch, Alexander Tacke, Frank Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis |
title | Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis |
title_full | Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis |
title_fullStr | Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis |
title_full_unstemmed | Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis |
title_short | Differential Gene Expression in Circulating CD14(+) Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis |
title_sort | differential gene expression in circulating cd14(+) monocytes indicates the prognosis of critically ill patients with sepsis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019484/ https://www.ncbi.nlm.nih.gov/pubmed/31906585 http://dx.doi.org/10.3390/jcm9010127 |
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