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Chitinase 3-like 1 is induced by Plasmodium falciparum malaria and predicts outcome of cerebral malaria and severe malarial anaemia in a case–control study of African children

机译:在非洲儿童的病例对照研究中,几丁质酶3样1由恶性疟原虫疟疾诱导,并预测脑疟疾和严重疟疾贫血的结果

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Background Severe and fatal malaria are associated with dysregulated host inflammatory responses to infection. Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein implicated in regulating immune responses. Expression and function of CHI3L1 in malaria infection were investigated. Methods Plasma levels of CHI3L1 were quantified in a case–control study of Ugandan children presenting with Plasmodium falciparum malaria. CHI3L1 levels were compared in children with uncomplicated malaria (UM; n?=?53), severe malarial anaemia (SMA; n?=?59) and cerebral malaria (CM; n?=?44) using the Kruskall Wallis-test, and evaluated for utility in predicting fatal (n?=?23) versus non-fatal (n?=?80) outcomes in severe disease using the Mann Whitney U test, receiver operating characteristic curves, and combinatorial analysis. Co-culture of P. falciparum with human peripheral blood mononuclear cells and the Plasmodium berghei ANKA experimental model of cerebral malaria were used to examine the role of CHI3L1 in severe malaria. Results In children presenting with falciparum malaria, CHI3L1 levels were increased in SMA and CM versus UM (p?
机译:背景严重和致命的疟疾与宿主对感染的炎症反应失调有关。几丁质酶3样1(CHI3L1)是一种分泌的糖蛋白,与调节免疫反应有关。研究了CHI3L1在疟疾感染中的表达和功能。方法在一项病例对照研究中,对患有恶性疟原虫疟疾的乌干达儿童进行定量研究,对CHI3L1的血浆水平进行定量。使用Kruskall Wallis检验比较了未合并疟疾(UM; n?=?53),严重疟疾(SMA; n?=?59)和脑疟疾(CM; n?=?44)患儿的CHI3L1水平,并使用Mann Whitney U检验,受试者工作特征曲线和组合分析评估了在严重疾病中致命(n≥23)与非致命(n≥80)结局的效用。恶性疟原虫与人外周血单个核细胞的共培养和伯氏疟原虫ANKA脑疟疾实验模型被用来检验CHI3L1在严重疟疾中的作用。结果在患有恶性疟疾的儿童中,与UM相比,SMA和CM中的CHI3L1水平升高(p <0.001)。在严重的疟疾病例中,就诊时的CHI3L1水平可预测随后的死亡(接受者工作特征曲线下的面积0.84 [95%CI 0.76-0.92]),并与其他宿主生物标志物组合使用,可高度预测死亡率(100%[85.7-100]) )和特异性(81.3%[71.3-88.3])。恶性疟原虫在体外刺激人外周血单个核细胞产生CHI3L1。在实验性脑疟疾中,血浆和脑组织中的CHI3L1增加,但是在该模型中,有针对性的Chi3l1缺失并未改变细胞因子的产生或存活。结论这些数据表明,在演示中测得的血浆CHI3L1与疟疾的严重程度相关,并预测了小儿SMA和CM的预后,但在所测试的模型中不支持CHI3L1在脑疟疾病理学中的因果作用。

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