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

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.

• Publication year

  2016

• Venue

  Scientific Reports

• Publication date

  2016-06-20

• Fields of study

  Medicine

• Identifiers
  DOI 10.1038/srep28006PMID 27320175PMCID 4913253
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2016cited by this paper
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  2015cited by this paper
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  2015cited by this paper
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  2014cited by this paper
• Levels of Circulating miR-133a Are Elevated in Sepsis and Predict Mortality in Critically Ill Patients

  2014cited by this paper
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  2014cited by this paper
• miR-191: an emerging player in disease biology

  2014cited by this paper
• Summary and discussion of : “ Controlling the False Discovery Rate : A Practical and Powerful Approach to Multiple Testing

  2014cited by this paper
• The TGF‐β‐inducible miR‐23a cluster attenuates IFN‐γ levels and antigen‐specific cytotoxicity in human CD8+ T cells

  2014cited by this paper
• MicroRNA-Containing T-Regulatory-Cell-Derived Exosomes Suppress Pathogenic T Helper 1 Cells

  2014cited by this paper
• Assessing sample and miRNA profile quality in serum and plasma or other biofluids.

  2013cited by this paper
• U6 is unsuitable for normalization of serum miRNA levels in patients with sepsis or liver fibrosis

  2013cited by this paper
• Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators.

  2013cited by this paper
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  2013cited by this paper
• MicroRNAs activate natural killer cells through Toll-like receptor signaling.

  2013cited by this paper
• The Impact of Hemolysis on Cell-Free microRNA Biomarkers

  2013cited by this paper
• Profiling Circulating MicroRNA Expression in Experimental Sepsis Using Cecal Ligation and Puncture

  2013cited by this paper
• Genome-Wide Sequencing of Cellular microRNAs Identifies a Combinatorial Expression Signature Diagnostic of Sepsis

  2013cited by this paper
• Circulating MicroRNA-150 Serum Levels Predict Survival in Patients with Critical Illness and Sepsis

  2013cited by this paper
• Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care

  2013cited by this paper
• Identification of circulating miRNA biomarkers based on global quantitative real-time PCR profiling

  2012cited by this paper
• Identification of circulating microRNAs as diagnostic biomarkers for use in multiple myeloma

  2012cited by this paper
• Serum miR-574-5p: A Prognostic Predictor of Sepsis Patients

  2012cited by this paper
• microRNA regulation of inflammatory responses.

  2012cited by this paper
• Four serum microRNAs identified as diagnostic biomarkers of sepsis

  2012cited by this paper
• Production and Characterization of Antifungal Compounds Produced by Lactobacillus plantarum IMAU10014

  2012cited by this paper
• MicroRNA-181b regulates NF-κB-mediated vascular inflammation.

  2012cited by this paper
• Predictors of survival in sepsis: what is the best inflammatory marker to measure?

  2012cited by this paper
• TLRs as miRNA receptors.

  2012cited by this paper
• Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides

  2012cited by this paper
• Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects

  2012cited by this paper
• Serum MicroRNA Signatures Identified by Solexa Sequencing Predict Sepsis Patients’ Mortality: A Prospective Observational Study

  2012cited by this paper
• MicroRNAs as components of regulatory networks controlling erythropoiesis

  2012cited by this paper
• Comparing the MicroRNA Spectrum between Serum and Plasma

  2012cited by this paper
• Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome

  2012cited by this paper
• Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells

  2011cited by this paper
• Blood Cell Origin of Circulating MicroRNAs: A Cautionary Note for Cancer Biomarker Studies

  2011cited by this paper
• The Role of MicroRNAs in Regulatory T Cells and in the Immune Response

  2011cited by this paper
• Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs

  2011cited by this paper
• Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma

  2011cited by this paper
• Impact of Cellular miRNAs on Circulating miRNA Biomarker Signatures

  2011cited by this paper
• Haemolysis during Sample Preparation Alters microRNA Content of Plasma

  2011cited by this paper
• Circulating microRNAs: Association with disease and potential use as biomarkers.

  2011cited by this paper
• Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development.

  2010cited by this paper
• Physiological and pathological roles for microRNAs in the immune system

  2010cited by this paper
• Serum miR-146a and miR-223 as potential new biomarkers for sepsis.

  2010cited by this paper
• A comparative study of common techniques used to measure haemolysis in stored red cell concentrates

  2010cited by this paper
• Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis.

  2010cited by this paper
• Sequencing technologies — the next generation

  2010cited by this paper
• Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992.

  2009cited by this paper
• Influence of hemolysis on routine clinical chemistry testing

  2009cited by this paper
• MicroRNAs: Target Recognition and Regulatory Functions

  2009cited by this paper
• The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo.

  2009cited by this paper
• MicroRNA Fingerprints Identify miR-150 as a Plasma Prognostic Marker in Patients with Sepsis

  2009cited by this paper
• miR-146a Is Critical for Endotoxin-induced Tolerance

  2009cited by this paper
• Circulating microRNAs as stable blood-based markers for cancer detection

  2008cited by this paper
• Detection of microRNA Expression in Human Peripheral Blood Microvesicles

  2008cited by this paper
• Sepsis: definition, epidemiology, and diagnosis

  2007cited by this paper
• Stress molecules in sepsis and systemic inflammatory response syndrome

  2007cited by this paper
• NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses

  2006cited by this paper
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  2006cited by this paper
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  2004cited by this paper
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  2004cited by this paper
• SEPSIS SYNDROMES: UNDERSTANDING THE ROLE OF INNATE AND ACQUIRED IMMUNITY

  2001cited by this paper
• Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care

  2001cited by this paper
• Controlling the false discovery rate: a practical and powerful approach to multiple testing

  1995cited by this paper
• Guidelines for the Use of Innovative Therapies in Sepsis

  1993cited by this paper
• Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.

  1992cited by this paper
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  1992cited by this paper
• New method for hemoglobin determination by using sodium lauryl sulfate (SLS).

  1982cited by this paper
• A method for determination of hemoglobin in plasma by near-ultraviolet spectrophotometry.

  1959cited by this paper

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  2023cites this paper
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  2023cites this paper
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  2022cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019influential citation
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• Extracellular Vesicles as Markers and Mediators in Sepsis

  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper