Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via Rudini 8, 20142, Milan, Italy.
Fondazione Filarete, Viale Ortles 22/4, 20139, Milan, Italy.
Crit Care. 2018 Nov 21;22(1):312. doi: 10.1186/s13054-018-2242-3.
Septic shock is the most severe complication of sepsis and this syndrome is associated with high mortality. Treatment of septic shock remains largely supportive of hemodynamics and tissue perfusion. Early changes in organ function assessed by the Sequential Organ Function Assessment (SOFA) score are highly predictive of the outcome. However, the individual patient's response to supportive therapy is very heterogeneous, and the mechanisms underlying this variable response remain elusive. The aim of the study was to investigate the transcriptome of whole blood in septic shock patients with different responses to early supportive hemodynamic therapy assessed by changes in SOFA scores within the first 48 h from intensive care unit (ICU) admission.
We performed whole blood RNA sequencing in 31 patients: 17 classified as responders (R) and 14 as non-responders (NR). Gene expression was investigated at ICU admission (time point 1, or T1), comparing R with NR [padj < 0.01; Benjamini-Hochberg (BH)] and over time from T1 to T2 (48 h later) in R and NR independently (paired analysis, padj < 0.01; BH). Then the differences in gene expression trends over time were evaluated (Mann-Whitney, P <0.01). To identify enriched biological processes, we performed an over-representation analysis based on a right-sided hypergeometric test with Bonferroni step-down as multiple testing correction (padj < 0.05).
At ICU admission, we did not identify differentially expressed genes (DEGs) between the two groups. In the transition from T1 to T2, the activation of genes involved in T cell-mediated immunity, granulocyte and natural killer (NK) cell functions, and pathogen lipid clearance was noted in the R group. Genes involved in acute inflammation were downregulated in both groups.
Within the limits of a small sample size, our results could suggest that early activation of genes of the adaptive immune response is associated with an improvement in organ function.
感染性休克是脓毒症最严重的并发症，该综合征与高死亡率相关。感染性休克的治疗仍然主要以支持血流动力学和组织灌注为主。序贯器官衰竭评估（SOFA）评分评估的器官功能早期变化对预后具有高度预测性。然而，个体患者对支持性治疗的反应非常不同，并且这种可变反应的机制仍然难以捉摸。本研究的目的是研究在重症监护病房（ICU）入院后 48 小时内通过 SOFA 评分评估的早期支持性血流动力学治疗反应不同的感染性休克患者全血的转录组。
我们对 31 名患者进行了全血 RNA 测序：17 名患者被归类为反应者（R），14 名患者为无反应者（NR）。在 ICU 入院时（时间点 1 或 T1）比较 R 与 NR [padj < 0.01；Benjamini-Hochberg（BH）]，并在 R 和 NR 中独立进行 T1 到 T2（48 小时后）的时间变化（配对分析，padj < 0.01；BH）。然后评估基因表达趋势随时间的差异（Mann-Whitney，P < 0.01）。为了识别富集的生物学过程，我们基于右偏超几何检验并使用 Bonferroni 逐步向下作为多重检验校正（padj < 0.05）进行了过表达分析。
在 ICU 入院时，我们没有在两组之间发现差异表达基因（DEGs）。在从 T1 到 T2 的转变过程中，R 组中观察到与 T 细胞介导的免疫、粒细胞和自然杀伤（NK）细胞功能以及病原体脂质清除相关的基因的激活。两组中与急性炎症相关的基因下调。
在小样本量的限制内，我们的结果可能表明，适应性免疫反应的早期基因激活与器官功能的改善相关。
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