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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

: Decker, S.O.; Sigl, A.; Grumaz, C.; Stevens, P.; Vainshtein, Y.; Zimmermann, S.; Weigand, M.A.; Hofer, S.; Sohn, K.; Brenner, T.

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International journal of molecular sciences 18 (2017), Nr.8, Art. 1796, 32 S.
ISSN: 1422-0067
ISSN: 1661-6596
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IGB ()

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.