Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
König, E.
Sensitivity and Specificity of Sepsis Markers derived from Circulating Nucleic Acids.
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2020. pp.
- Autor*innen der Med Uni Graz:
- König Elisabeth
- Betreuer*innen:
- Krause Robert
- Leitner-Meyer Eva
- Altmetrics:
- Abstract:
- Background Sepsis is a life-threatening host response to infection. We are investigating circulating nucleic acids (CNA) as possible early diagnostic markers (motifs). The diagnostic value of CNA has been suspected since the 1970s, but only next-generation sequencing has made it possible to characterize CNA in detail. We hypothesize that specific DNA motifs exist in the plasma of patients who are developing sepsis, which can be used as markers for predicting sepsis at an early stage of the disease. These markers can be identified via Real-time PCR (qPCR) assays. Material and methods In this study, CNA were isolated and amplified from plasma of patients with sepsis, drawn concomitantly to positive blood cultures and compared with samples from controls. Via high-throughput Illumina paired-end sequencing with subsequent bioinformatics analysis of the CNA molecules, differences in the sets of CNA patterns between healthy controls and patients were identified. Subsequently, determination of these motifs by qPCR has been established as a method to predict sepsis at an early onset. Results We identified 24 molecular markers, based on circulating nucleic acids (CNA) which in combination can be used in a qPCR assay to identify the presence of human sepsis. Sepsis group included 147 samples from 69 patients who met SEPSIS-3 criteria. Control cohort consisted of 71 samples from 58 people including healthy volunteers as well as influenza and lymphoma patients. Overall balanced accuracy of the qPCR was 89.6% with a sensitivity of 93.8 % and specificity of 85.4%. Conclusion As our markers are host-based, they can be used to capture bacterial as well as fungal sepsis, unlike the current PCR-based tests, which require species-specific primer sets for each organism causing human sepsis.