Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.
Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.
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内皮细胞转录组学分析鉴定重症疟疾和脑型疟疾的生物标志物。
DOI：
10.1172/jci.insight.172845
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发表时间：
2023-11-22
期刊：
影响因子：
8
通讯作者：
Rodriguez, Ana
中科院分区：
文献类型：
--
作者：
Gomes, Claudia;Varo, Rosauro;Duran-Frigola, Miquel;Sitoe, Antonio;Bila, Rubio;Machevo, Sonia;Mayor, Alfredo;Bassat, Quique;Rodriguez, Ana
疟疾可以从一种简单的感染迅速发展成一种危及生命的严重疾病。然而，早期症状的非特异性通常使得难以识别处于发展严重疾病的高风险的患者。此外，最可怕的疟疾并发症之一-脑型疟疾-诊断具有挑战性，往往导致治疗延误，可能导致不良后果。为了确定候选生物标志物的预后和/或诊断严重和脑型疟疾，我们分析了人脑微血管内皮细胞的转录组反应感染恶性疟原虫的红细胞。候选人在来自莫桑比克的一组儿童疟疾患者的血浆样本中进行了验证，结果鉴定出几种能够区分单纯性疟疾和严重疟疾的标志物，其中最有效的是金属肽酶ADAMTS 18。另外两种生物标志物，血管生成素样-4和抑制素-βE能够区分严重疟疾组中的脑型疟疾儿童，在生物标志物签名中组合后显示出增加的灵敏度。在患有严重疟疾和脑型疟疾的儿童血浆中预测的候选生物标志物的验证强调了这种转录组学方法的力量，并表明对恶性疟原虫感染的红细胞的特异性内皮反应与严重疟疾的病理生理学有关。
Malaria can quickly progress from an uncomplicated infection into a life-threatening severe disease. However, the unspecificity of early symptoms often makes it difficult to identify patients at high risk of developing severe disease. Additionally, one of the most feared malaria complications — cerebral malaria — is challenging to diagnose, often resulting in treatment delays that can lead to adverse outcomes. To identify candidate biomarkers for the prognosis and/or diagnosis of severe and cerebral malaria, we have analyzed the transcriptomic response of human brain microvascular endothelial cells to erythrocytes infected with Plasmodium falciparum. Candidates were validated in plasma samples from a cohort of pediatric patients with malaria from Mozambique, resulting in the identification of several markers with capacity to distinguish uncomplicated from severe malaria, the most potent being the metallopeptidase ADAMTS18. Two other biomarkers, Angiopoietin-like-4 and Inhibin-βE were able to differentiate children with cerebral malaria within the severe malaria group, showing increased sensitivity after combination in a biomarker signature. The validation of the predicted candidate biomarkers in plasma of children with severe and cerebral malaria underscores the power of this transcriptomic approach and indicates that a specific endothelial response to P. falciparum–infected erythrocytes is linked to the pathophysiology of severe malaria.
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影响因子：
11.8
作者：
Gupta H;Rubio M;Sitoe A;Varo R;Cisteró P;Madrid L;Cuamba I;Jimenez A;Martiáñez-Vendrell X;Barrios D;Pantano L;Brimacombe A;Bustamante M;Bassat Q;Mayor A
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3
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通讯作者：
Kain, Kevin C.
影响因子：
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作者：
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