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Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis

Background: Sepsis is a life-threatening syndrome, resulting from a dysbalanced host response to infection. However, especially the early, pro-inflammatory immune response in sepsis is similar to other inflammatory conditions without infectious cause, e.g., trauma or surgery. This aspect challenges...

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Autores principales: Hildebrand, Dagmar, Decker, Sebastian O., Koch, Christian, Schmitt, Felix C. F., Ruhrmann, Sophie, Schneck, Emmanuel, Sander, Michael, Weigand, Markus Alexander, Brenner, Thorsten, Heeg, Klaus, Uhle, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663974/
https://www.ncbi.nlm.nih.gov/pubmed/31396491
http://dx.doi.org/10.3389/fcimb.2019.00267
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author Hildebrand, Dagmar
Decker, Sebastian O.
Koch, Christian
Schmitt, Felix C. F.
Ruhrmann, Sophie
Schneck, Emmanuel
Sander, Michael
Weigand, Markus Alexander
Brenner, Thorsten
Heeg, Klaus
Uhle, Florian
author_facet Hildebrand, Dagmar
Decker, Sebastian O.
Koch, Christian
Schmitt, Felix C. F.
Ruhrmann, Sophie
Schneck, Emmanuel
Sander, Michael
Weigand, Markus Alexander
Brenner, Thorsten
Heeg, Klaus
Uhle, Florian
author_sort Hildebrand, Dagmar
collection PubMed
description Background: Sepsis is a life-threatening syndrome, resulting from a dysbalanced host response to infection. However, especially the early, pro-inflammatory immune response in sepsis is similar to other inflammatory conditions without infectious cause, e.g., trauma or surgery. This aspect challenges the value of current biomarkers for diagnosis, as these are often broadly induced. We earlier identified Delta-like Protein 1 (DLL1), a canonical Notch ligand, to be released from monocytes upon bacterial stimulation. Considering the importance of monocytes in the pathophysiology of sepsis, we hypothesized that this mechanism might occur also in the clinical setting and DLL1 might serve as a biomarker of life-threatening bacterial infection. Methods: We combined samples from three different studies, including subgroups of patients with sepsis (n = 80), surgical patients (n = 50), trauma patients (n = 36), as well as healthy controls (n = 50). We assessed plasma concentrations of DLL1 using ELISA. We performed Area-under-receiver-operator-curve (AUROC) analysis to evaluate the diagnostic performance of DLL1 compared to leucocytes, C-reactive protein (CRP), and procalcitonin (PCT). Results: Plasma concentrations of DLL1 were strongly elevated already at sepsis onset and maintained elevated until day 7. In contrast, neither surgical patients nor patients after severe trauma presented with elevated levels, while conventional biomarkers of inflammation (e.g., leucocytes and CRP), responded. AUROC analysis revealed a cut-off of 30 ng/ml associated with the best diagnostic performance, yielding a superior accuracy of 91% for DLL1, compared to 75, 79, and 81% for CRP, leucocytes, and PCT. Conclusion: DLL1 is a novel host-derived biomarker for the diagnosis of sepsis with a better performance compared to established ones, most likely due to its high robustness in non-infectious inflammatory responses. Clinical Trial Registration: POCSEP-Trial DRKS00008090; MIRSI DRKS00005463; SPRINT DRKS00010991.
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spelling pubmed-66639742019-08-08 Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis Hildebrand, Dagmar Decker, Sebastian O. Koch, Christian Schmitt, Felix C. F. Ruhrmann, Sophie Schneck, Emmanuel Sander, Michael Weigand, Markus Alexander Brenner, Thorsten Heeg, Klaus Uhle, Florian Front Cell Infect Microbiol Cellular and Infection Microbiology Background: Sepsis is a life-threatening syndrome, resulting from a dysbalanced host response to infection. However, especially the early, pro-inflammatory immune response in sepsis is similar to other inflammatory conditions without infectious cause, e.g., trauma or surgery. This aspect challenges the value of current biomarkers for diagnosis, as these are often broadly induced. We earlier identified Delta-like Protein 1 (DLL1), a canonical Notch ligand, to be released from monocytes upon bacterial stimulation. Considering the importance of monocytes in the pathophysiology of sepsis, we hypothesized that this mechanism might occur also in the clinical setting and DLL1 might serve as a biomarker of life-threatening bacterial infection. Methods: We combined samples from three different studies, including subgroups of patients with sepsis (n = 80), surgical patients (n = 50), trauma patients (n = 36), as well as healthy controls (n = 50). We assessed plasma concentrations of DLL1 using ELISA. We performed Area-under-receiver-operator-curve (AUROC) analysis to evaluate the diagnostic performance of DLL1 compared to leucocytes, C-reactive protein (CRP), and procalcitonin (PCT). Results: Plasma concentrations of DLL1 were strongly elevated already at sepsis onset and maintained elevated until day 7. In contrast, neither surgical patients nor patients after severe trauma presented with elevated levels, while conventional biomarkers of inflammation (e.g., leucocytes and CRP), responded. AUROC analysis revealed a cut-off of 30 ng/ml associated with the best diagnostic performance, yielding a superior accuracy of 91% for DLL1, compared to 75, 79, and 81% for CRP, leucocytes, and PCT. Conclusion: DLL1 is a novel host-derived biomarker for the diagnosis of sepsis with a better performance compared to established ones, most likely due to its high robustness in non-infectious inflammatory responses. Clinical Trial Registration: POCSEP-Trial DRKS00008090; MIRSI DRKS00005463; SPRINT DRKS00010991. Frontiers Media S.A. 2019-07-23 /pmc/articles/PMC6663974/ /pubmed/31396491 http://dx.doi.org/10.3389/fcimb.2019.00267 Text en Copyright © 2019 Hildebrand, Decker, Koch, Schmitt, Ruhrmann, Schneck, Sander, Weigand, Brenner, Heeg and Uhle. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Hildebrand, Dagmar
Decker, Sebastian O.
Koch, Christian
Schmitt, Felix C. F.
Ruhrmann, Sophie
Schneck, Emmanuel
Sander, Michael
Weigand, Markus Alexander
Brenner, Thorsten
Heeg, Klaus
Uhle, Florian
Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis
title Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis
title_full Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis
title_fullStr Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis
title_full_unstemmed Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis
title_short Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis—Results From a Combinational Secondary Analysis
title_sort host-derived delta-like canonical notch ligand 1 as a novel diagnostic biomarker for bacterial sepsis—results from a combinational secondary analysis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663974/
https://www.ncbi.nlm.nih.gov/pubmed/31396491
http://dx.doi.org/10.3389/fcimb.2019.00267
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