Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.
Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.
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儿童重症流感多器官功能障碍综合征表型的转录组学分析
DOI：
10.3389/fimmu.2023.1220028
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
流感病毒造成了全球巨大的疾病负担，尤其是对儿童。多器官功能障碍综合征（MODS）是严重流感感染的致命并发症。我们测量了469个生物学上合理的候选基因的RNA表达，这些基因在患有严重流感病毒感染并伴或不伴MODS的北美儿科重症监护病房的儿童中进行。191名流感感染儿童（中位年龄6.4岁，IQR：2.2，11）的全血样本在入院后27小时内采集; 45名儿童在大约7天后采集第二份血液样本。将提取的RNA与NanoString mRNA探针杂交，计数归一化，并使用控制年龄和细菌共感染的线性模型（FDR q<0.05）进行分析。比较入院时收集的儿科样本，与MODS恢复更快的儿童（n=27）相比，MODS持续时间≥7天的儿童（n=38; 9例死亡）与中性粒细胞脱粒相关的9种mRNA转录物（RETN、TCN 1、OLFM 4、MMP 8、LCN 2、BPI、LTF、S100 A12、GUSB）显著上调。与恢复的患者相比，早期样本中存在的这些中性粒细胞转录物预测了延长的MODS或死亡，然而，在配对的纵向样本中，它们随时间的推移没有差异表达。相反，参与蛋白质代谢和/或适应性免疫信号通路的5个基因（RPL 3、MRPL 3、HLA-DMB、EEF 1G、CD 8A）与MODS在一周内恢复相关。因此，中性粒细胞脱颗粒基因的早期表达增加表明流感感染儿童的临床结局较差，这与流感、脓毒症和急性呼吸窘迫综合征成人队列的报告一致。
Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
5.3
作者：
Liu S;Huang Z;Deng X;Zou X;Li H;Mu S;Cao B
通讯作者：
Cao B
影响因子：
8.8
作者：
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通讯作者：
Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network PICFlu Study Investigators
影响因子：
3.9
作者：
Galmiche, Louise;Serre, Valerie;Roetig, Agnes
通讯作者：
Roetig, Agnes
影响因子：
20.3
作者：
Ramilo, Octavio;Allman, Windy;Chaussabel, Damien
通讯作者：
Chaussabel, Damien