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
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 nec...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 August 2017
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| In: |
International journal of molecular sciences
Year: 2017, Volume: 18, Issue: 8 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms18081796 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3390/ijms18081796 Verlag, kostenfrei, Volltext: http://www.mdpi.com/1422-0067/18/8/1796 
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| Author Notes: | Sebastian O. Decker, Annette Sigl, Christian Grumaz, Philip Stevens, Yevhen Vainshtein, Stefan Zimmermann, Markus A. Weigand, Stefan Hofer, Kai Sohn and Thorsten Brenner |
| Summary: | 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. |
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| Item Description: | Gesehen am 04.01.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms18081796 |