Differential expression of plasma miR-146a in sepsis patients compared with non-sepsis-SIRS patients

Abstract

Sepsis is a subtype of systemic inflammatory response syndrome (SIRS), which is characterized by infection. Circulating microRNAs (miRNAs), including miR-150, miR-146a and miR-223, are potential biomarkers of sepsis. In this study, we demonstrated that measuring the relative expression of miR-146a/U6 in plasma, using the 2−ΔΔCt method, provides a method for differentiating between sepsis and non-sepsis-SIRS. We observed a significant increase in miR-146a expression in the initial cohort of 6 non-sepsis-SIRS patients compared to the 4 sepsis patients (P=0.01) and in the second cohort of 8 non-sepsis-SIRS patients compared to the 10 sepsis patients (P=0.027). Additionally, we identified that sodium citrate and ethylenediaminetetraacetic acid (EDTA) K2 may be used as anticoagulant reagents. Generation of a standard curve is not necessary in these diagnostic tests, unless the standard of normalization is carefully selected. Thus we provide more detailed guidance for the clinical use of circulating miRNA biomarkers.

Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology

“…Key among the dysregulated miRNAs identified in this study is miR-146a, supporting the downregulation observed in a pair of past reports of human sepsis [26, 28]. miR-146a is rich with targets capable of immune modulation.…”

MicroRNA's are novel biomarkers in sepsis – A systematic review

“…None of the studies specified the duration of symptoms before inclusion. Nine studies did the initial blood samples at the admission to the ICU [15,16,18,19,25] or within 24 h after admission to the ICU [20,21,23,24]. One study did baseline measurements before LPS infusion [17] and one study did not apply a time of sample collection [22].…”

“…In 8/13 studies [16e18,20,23e26] the authors searched mainly for pre-defined miRs while in the rest of the studies [15,19,21,22,27] a pre-experimental testing on survivors/non-survivors or animals were made before determining which miRs to investigate in the validation population look. Four studies [15,20,23,25] compared patients with sepsis with patients with SIRS. One study [17] analysed changes in miR-expression in three male healthy volunteers after endotoxemia induction, using lipopolysaccharides from gram positive bacteria to simulate sepsis.…”

Role of extracellular and intracellular microRNAs in sepsis

“…Subsequently, another study, using RT-PCR, examined the differential expression of miR-146a in plasma samples of 14 non-sepsis SIRS patients and 14 sepsis patients. The investigators observed higher levels of serum miR-146a in non-sepsis SIRS patients compared to sepsis patients [32]. Hence, these studies suggest that miR-146a and miR-223 may be optimal diagnostic tools for sepsis.…”