Format

Send to

Choose Destination
Int J Mol Sci. 2017 Aug 18;18(8). pii: E1796. doi: 10.3390/ijms18081796.

Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock-Results of a Combined Clinical and Experimental Investigation.

Author information

1
Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. Sebastian.Decker@med.uni-heidelberg.de.
2
Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. Annette.Sigl@gmx.de.
3
Fraunhofer IGB, 12, Nobelstraße, D-70569 Stuttgart, Germany. Christian.Grumaz@igb.fraunhofer.de.
4
Fraunhofer IGB, 12, Nobelstraße, D-70569 Stuttgart, Germany. philip.stevens@noscendo.com.
5
Noscendo GmbH, 9, Meitnerstraße, D-70563 Stuttgart, Germany. philip.stevens@noscendo.com.
6
Fraunhofer IGB, 12, Nobelstraße, D-70569 Stuttgart, Germany. yevhen.vainshtein@igb.fraunhofer.de.
7
Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 324, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. Stefan.Zimmermann@med.uni-heidelberg.de.
8
Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. Markus.Weigand@med.uni-heidelberg.de.
9
Department of Anesthesiology, Westpfalzklinikum, 1, Hellmut-Hartert-Straß, D-67655 Kaiserslautern, Germany. shofer@westpfalz-klinikum.de.
10
Fraunhofer IGB, 12, Nobelstraße, D-70569 Stuttgart, Germany. Kai.Sohn@igb.fraunhofer.de.
11
Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. Thorsten.Brenner@med.uni-heidelberg.de.

Abstract

Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of β-d-glucan, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A, and mid-regional proadrenomedullin (MR-proADM) were evaluated in 50 septic patients at six consecutive time points within 28 days after sepsis onset. Furthermore, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% (n = 11) of patients suffered from a fungal infection. An NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene which is upregulated early after an epithelial infection with Candida spp. In summary, an NGS-based diagnostic approach was able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of MR-proADM and IL-17A. In addition, ADM was identified as an early target gene in response to epithelial infections with Candida spp.

KEYWORDS:

">d-glucan; interleukin-17A; mid-regional proadrenomedullin; mycoses; next-generation sequencing; sepsis; septic shock; β-

PMID:
28820494
PMCID:
PMC5578184
DOI:
10.3390/ijms18081796
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center