Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS).
Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS).
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DOI：
10.1038/srep28006
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发表时间：
2016-06-20
影响因子：
4.6
通讯作者：
Llewelyn MJ
中科院分区：
文献类型：
--
作者：
Caserta S;Kern F;Cohen J;Drage S;Newbury SF;Llewelyn MJ
人类的全身性炎症可由感染或非感染性过程触发，称为非感染性全身炎症反应综合征(SIRS)。MicroRNA调节包括炎症在内的细胞过程，并可能在血液中检测到。我们的目标是建立明确的原则证明，在脓毒症和非感染性SIRS期间，循环中的microRNA受到不同的影响。研究对象包括重症(n = 21例)或非重症(n = 8例)腹内脓毒症；重症(n = 23例)或非重症(n = 21例)非感染性SIRS；或无SIRS(n = 16例)。采用下一代测序和定量逆转录聚合酶链式反应(qRT-PCR)检测血浆microRNAs。与非SIRS患者相比，SIRS患者血液中可检测到的 = (N MiRNAs 116)普遍上调。在非感染性SIRS和脓毒症患者中，CIR-miRNAs的表达水平分别是非感染性SIRS和脓毒症患者的2.64(IQR2.10~3.29)和1.52(IQR1.15~1.92)倍(p <； 0.0001)，因此脓毒症患者CIR-miRNAs的含量低于SIRS。6个CIR-miRNAs(miR-30d-5p、miR-30a-5p、miR-192-5p、miR-26a-5p、miR-23a-5p、miR-191-5p)对严重脓毒症和严重SIRS的鉴别(ROC曲线的AUC值为0.742~0.917)。CIR-miRNA水平与促炎细胞因子(IL-1、IL-6等)呈负相关。因此，在危重病患者中，脓毒症和非感染性SIRS与CIR-miRNAs的显著差异变化有关。CIR-miRNAs可能是炎症的调节因子，有必要作为诊断和治疗的靶点进行彻底的评估。
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.