Immune-response patterns and next generation sequencing diagnostics for the detection of mycoses in patients with septic shock

• Verfasst von: Decker, Sebastian [VerfasserIn]
• Verfasst von: Weigand, Markus A. [VerfasserIn]
• Verfasst von: Brenner, Thorsten [VerfasserIn]
• Titel: Immune-response patterns and next generation sequencing diagnostics for the detection of mycoses in patients with septic shock
• Titelzusatz: results of a combined clinical and experimental investigation
• Verf.angabe: Sebastian O. Decker, Annette Sigl, Christian Grumaz, Philip Stevens, Yevhen Vainshtein, Stefan Zimmermann, Markus A. Weigand, Stefan Hofer, Kai Sohn and Thorsten Brenner
• E-Jahr: 2017
• Jahr: 18 August 2017
• Umfang: 14 S.
• Fussnoten: Gesehen am 04.01.2018
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2017
• Band/Heft Quelle: 18(2017,8) Artikel-Nummer 1796, 32 Seiten
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms18081796
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ">d</span>-glucan
• Sach-SW: interleukin-17A
• Sach-SW: mid-regional proadrenomedullin
• Sach-SW: mycoses
• Sach-SW: next-generation sequencing
• Sach-SW: sepsis
• Sach-SW: septic shock
• Sach-SW: β-<span style="font-variant: small-caps
• K10plus-PPN: 1566851947
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

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.