Int. J. Mol. Sci. 2017, 18(8), 1796; https://doi.org/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
Sebastian O. Decker 1, Annette Sigl 1, Christian Grumaz 2, Philip Stevens 2,3, Yevhen Vainshtein 2
, Stefan Zimmermann 4, Markus A. Weigand 1, Stefan Hofer 5, Kai Sohn 2,† and Thorsten Brenner 1,†,*
, Stefan Zimmermann 4, Markus A. Weigand 1, Stefan Hofer 5, Kai Sohn 2,† and Thorsten Brenner 1,†,*
1
Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany
2
Fraunhofer IGB, 12, Nobelstraße, D-70569 Stuttgart, Germany
3
Noscendo GmbH, 9, Meitnerstraße, D-70563 Stuttgart, Germany
4
Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 324, Im Neuenheimer Feld, D-69120 Heidelberg, Germany
5
Department of Anesthesiology, Westpfalzklinikum, 1, Hellmut-Hartert-Straß, D-67655 Kaiserslautern, Germany
†
Thorsten Brenner and Kai Sohn share senior authorship.
*
Author to whom correspondence should be addressed.
Received: 14 July 2017 / Revised: 12 August 2017 / Accepted: 14 August 2017 / Published: 18 August 2017
(This article belongs to the Special Issue Sepsis)
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. View Full-TextKeywords:
mid-regional proadrenomedullin; interleukin-17A; β-d-glucan; next-generation sequencing; mycoses; sepsis; septic shock
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Decker, S.O.; Sigl, A.; Grumaz, C.; Stevens, P.; Vainshtein, Y.; Zimmermann, S.; Weigand, M.A.; Hofer, S.; Sohn, K.; Brenner, T. 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. Int. J. Mol. Sci. 2017, 18, 1796.
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