Caserta, Stefano, Kern, Florian, Cohen, Jonathan, Drage, Stephen, Newbury, Sarah F and Llewelyn, Martin J (2016) Circulating plasma microRNAs can differentiate human sepsis and Systemic Inflammatory Response Syndrome (SIRS). Scientific Reports, 6. p. 28006. ISSN 2045-2322

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Abstract

Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets.

Item Type:	Article
Additional Information:	Supplementary data available at http://www.nature.com/articles/srep28006
Keywords:	MicroRNAs, Systemic inflammation, Sepsis, SIRS, Circulating miRNAs, Human disease, Sepsis biomarker
Schools and Departments:	Brighton and Sussex Medical School > Brighton and Sussex Medical School Brighton and Sussex Medical School > Global Health and Infection Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects:	Q Science Q Science > QH Natural history > QH0301 Biology > QH0324 Methods of research. Technique. Experimental biology Q Science > QH Natural history > QH0301 Biology R Medicine R Medicine > R Medicine (General) > R852 Research. Experimentation R Medicine > RB Pathology
Depositing User:	Stefano Caserta
Date Deposited:	28 Jun 2016 15:24
Last Modified:	21 Sep 2017 08:54
URI:	http://srodev.sussex.ac.uk/id/eprint/61765

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