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Enquiring beneath the surface: can a gene expression assay shed light into the heterogeneity among newborns with neonatal encephalopathy?
Pediatric Research ( IF 3.6 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41390-020-0764-2
Rafael Balada 1 , Cristian Tebé 2 , Marisol León 3 , Gemma Arca 3, 4, 5 , Miguel Alsina 3 , Alba-Aina Castells 1, 6, 7 , Soledad Alcántara 1, 7, 8 , Alfredo Garcia-Alix 5, 9, 10, 11
Affiliation  

Background We aimed to assess whether a gene expression assay provided insights for understanding the heterogeneity among newborns affected by neonatal encephalopathy (NE). Methods Analysis by RT-qPCR of the mRNA expression of candidate genes in whole blood from controls ( n = 34) and NE ( n = 24) patients at <6, 12, 24, 48, 72 and 96 h of life, followed by determination of differences in gene expression between conditions and correlation with clinical variables. Results During the first 4 days of life, MMP9, PPARG, IL8, HSPA1A and TLR8 were more expressed and CCR5 less expressed in NE patients compared to controls. MMP9 and PPARG increased and CCR5 decreased in moderate/severe NE patients compared to mild. At 6–12 h of life, increased IL8 correlated with severe NE and death, decreased CCR5 correlated with chorioamnionitis and increased HSPA1A correlated with expanded multiorgan dysfunction, severe NE and female sex. Conclusions MMP9, PPARG and CCR5 mRNA expression within first days of life correlates with the severity of NE. At 6–12 h, IL8 and HSPA1A are good reporters of clinical variables in NE patients. HSPA1A may have a role in the sexual dimorphism observed in NE. CCR5 is potentially involved in the link between severe NE and chorioamnionitis.

中文翻译:

深入探究:基因表达分析能否揭示新生儿脑病新生儿的异质性?

背景 我们旨在评估基因表达检测是否为了解受新生儿脑病 (NE) 影响的新生儿的异质性提供了见解。方法通过 RT-qPCR 分析对照 (n = 34) 和 NE (n = 24) 患者在<6、12、24、48、72 和 96 小时的全血中候选基因的 mRNA 表达,然后确定条件之间基因表达的差异以及与临床变量的相关性。结果 在生命的前 4 天,与对照组相比,NE 患者的 MMP9、PPARG、IL8、HSPA1A 和 TLR8 表达更多,而 CCR5 表达更少。与轻度相比,中度/重度 NE 患者的 MMP9 和 PPARG 增加而 CCR5 降低。在生命的 6-12 小时,增加的 IL8 与严重的 NE 和死亡相关,CCR5 降低与绒毛膜羊膜炎相关,HSPA1A 升高与多器官功能障碍、严重 NE 和女性相关。结论 生命最初几天内 MMP9、PPARG 和 CCR5 mRNA 的表达与 NE 的严重程度相关。在 6-12 小时,IL8 和 HSPA1A 是 NE 患者临床变量的良好报告者。HSPA1A 可能在 NE 中观察到的性别二态性中起作用。CCR5 可能与严重 NE 和绒毛膜羊膜炎之间的联系有关。
更新日期:2020-01-17
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