Background. Cerebral malaria (CM), a reversible encephalopathy affecting young children, is a medical emergency requiring rapid clinical assessment and treatment. However, understanding of the genes/proteins and the biological pathways involved in the disease outcome is still limited. Methods. We have performed a whole transcriptomic analysis of blood samples from Malian children with CM or uncomplicated malaria (UM). Hierarchical clustering and pathway, network, and upstream regulator analyses were performed to explore differentially expressed genes (DEGs). We validated gene expression for 8 genes using real-time quantitative PCR (RT-qPCR). Plasma levels were measured for IP-10/CXCL10 and IL-18. Results. A blood RNA signature including 538 DEGs (, adjusted value ≤ 0.01) allowed to discriminate between CM and UM. Ingenuity Pathway Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed novel genes and biological pathways related to immune/inflammatory responses, erythrocyte alteration, and neurodegenerative disorders. Gene expressions of CXCL10, IL12RB2, IL18BP, IL2RA, AXIN2, and NET were significantly lower in CM whereas ARG1 and SLC6A9 were higher in CM compared to UM. Plasma protein levels of IP-10/CXCL10 were significantly lower in CM than in UM while levels of IL-18 were higher. Interestingly, among children with CM, those who died from a complication of malaria tended to have higher concentrations of IP-10/CXCL10 and IFN-γ than those who recovered. Conclusions. This study identified some new factors and mechanisms that play crucial roles in CM and characterized their respective biological pathways as well as some upstream regulators.

中文翻译：

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通过血液转录组学特征了解人类脑型疟疾：红细胞改变、免疫/炎症失调和脑功能障碍的证据。

背景。脑疟疾 (CM) 是一种影响幼儿的可逆性脑病，是一种需要快速临床评估和治疗的医疗紧急情况。然而，对与疾病结果有关的基因/蛋白质和生物学途径的了解仍然有限。方法。我们对患有 CM 或单纯性疟疾 (UM) 的马里儿童的血液样本进行了完整的转录组分析。进行分层聚类和通路、网络和上游调节器分析以探索差异表达基因 (DEG)。我们使用实时定量 PCR (RT-qPCR) 验证了 8 个基因的基因表达。测量了 IP-10/CXCL10 和 IL-18 的血浆水平。结果。包括 538 度的血液 RNA 特征（,调整值 ≤ 0.01) 允许区分 CM 和 UM。Ingenuity Pathway Analysis (IPA) 和京都基因和基因组百科全书 (KEGG) 揭示了与免疫/炎症反应、红细胞改变和神经退行性疾病相关的新基因和生物学通路。与 UM 相比，CM 中 CXCL10、IL12RB2、IL18BP、IL2RA、AXIN2 和 NET 的基因表达显着降低，而 ARG1 和 SLC6A9 在 CM 中更高。CM 中 IP-10/CXCL10 的血浆蛋白水平显着低于 UM，而 IL-18 水平则更高。有趣的是，在患有 CM 的儿童中，死于疟疾并发症的儿童的 IP-10/CXCL10 和 IFN- γ浓度往往高于康复者。结论. 本研究确定了一些在 CM 中起关键作用的新因素和机制，并描述了它们各自的生物学途径以及一些上游调节因子。