Centre for Perinatal Neuroscience, Imperial College London, London, United
Neonatal Unit, Università degli Studi della Campania "Luigi Vanvitelli,", Naples,
Neonatology. 2019;115(1):68-76. doi: 10.1159/000492420. Epub 2018 Oct 10.
Variable responses to hypothermic neuroprotection are related to the clinical heterogeneity of encephalopathic babies; hence better disease stratification may facilitate the development of individualized neuroprotective therapies.
We examined if whole blood gene expression analysis can identify specific transcriptome profiles in neonatal encephalopathy.
We performed next-generation sequencing on whole blood RNA from 12 babies with neonatal encephalopathy and 6 time-matched healthy term babies. Genes significantly differentially expressed between encephalopathic and control babies were identified. This set of genes was then compared to the host RNA response in septic neonates and subjected to pathway analysis.
We identified 950 statistically significant genes discriminating perfectly between healthy controls and neonatal encephalopathy. The major pathways in neonatal encephalopathy were axonal guidance signaling (p = 0.0009), granulocyte adhesion and diapedesis (p = 0.003), IL-12 signaling and production in macrophages (p = 0.003), and hypoxia-inducible factor 1α signaling (p = 0.004). There were only 137 genes in common between neonatal encephalopathy and bacterial sepsis sets.
Babies with neonatal encephalopathy have striking differences in gene expression profiles compared with healthy control and septic babies. Gene expression profiles may be useful for disease stratification and for developing personalized neuroprotective therapies.
低温神经保护的反应具有变异性，与脑病婴儿的临床异质性有关；因此，更好的疾病分层可能有助于个体化神经保护治疗的发展。
我们研究了全血基因表达分析是否可以识别新生儿脑病中的特定转录组谱。
我们对 12 例新生儿脑病和 6 例时间匹配的健康足月婴儿的全血 RNA 进行了下一代测序。确定了在脑病婴儿和对照婴儿之间差异表达的基因。将这组基因与脓毒症新生儿的宿主 RNA 反应进行比较，并进行通路分析。
我们确定了 950 个在健康对照组和新生儿脑病之间具有统计学意义的差异表达基因。新生儿脑病的主要途径是轴突导向信号（p = 0.0009）、粒细胞黏附和渗出（p = 0.003）、巨噬细胞中 IL-12 信号和产生（p = 0.003）以及缺氧诱导因子 1α 信号（p = 0.004）。在新生儿脑病和细菌性败血症组之间只有 137 个基因是共同的。
与健康对照组和细菌性败血症组相比，新生儿脑病婴儿的基因表达谱存在显著差异。基因表达谱可能有助于疾病分层和开发个体化神经保护治疗。
