Circulating plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS)

Caserta, Stefano; Kern, Florian; Cohen, Jonathan; Drage, Stephen; Newbury, Sarah F.; Llewelyn, Martin J.

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.

Citation

Caserta, S., Kern, F., Cohen, J., Drage, S., Newbury, S. F., & Llewelyn, M. J. (2016). Circulating plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS). Scientific reports, 6(1), Article 28006. https://doi.org/10.1038/srep28006

• Journal Article Type: Article
• Acceptance Date: May 18, 2016
• Online Publication Date: Jun 20, 2016
• Publication Date: 2016-09
• Deposit Date: Feb 22, 2018
• Publicly Available Date: Oct 27, 2022
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 1
• Article Number: 28006
• DOI: https://doi.org/10.1038/srep28006
• Keywords: Multidisciplinary
• Public URL: https://hull-repository.worktribe.com/output/620143
• Publisher URL: https://www.nature.com/articles/srep28006
• Related Public URLs: https://www.research.ed.ac.uk/portal/en/publications/circulating-plasma-micrornas-can-differentiate-human-sepsis-and-systemic-inflammatory-response-syndrome-sirs(68338304-ea5f-483d-8909-fe4b5b8cab94).html