Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury.
Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury.
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DOI：
10.1038/s41426-018-0105-2
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发表时间：
2018-06-06
影响因子：
13.2
通讯作者：
Anstey NM
中科院分区：
文献类型：
--
作者：
Barber BE;Grigg MJ;Piera KA;William T;Cooper DJ;Plewes K;Dondorp AM;Yeo TW;Anstey NM
诺氏疟原虫遍布东南亚，是马来西亚人患疟疾的最常见原因。人类严重疾病的特征是寄生虫生物量高，红细胞变形性降低，内皮细胞激活和微血管功能障碍。然而，血管内溶血和一氧化氮(NO)依赖的内皮功能障碍是严重恶性疟疾的重要特征，它们在急性肾损伤(AKI)中的作用尚未得到评估。在患有严重疟疾(n = 48)和非严重疟疾(n = 154)的住院马来西亚成年人和健康对照组(n = 50)中，我们测量了无细胞血红蛋白(CFHb)，并评估了与内皮韦伯-帕拉德小体(WPB)成分、血管生成素-2和骨保护素、内皮和微血管功能以及其他疾病严重程度标志的相关性。在诺氏疟疾患者中，CFHb与疾病严重程度成比例增加，而且比同一研究队列中先前报道的严重恶性疟疾患者的CFHb增加的程度更大。在诺氏疟疾中，CFHb与寄生虫血症有关，并与血管生成素-2和护骨素独立相关。与血管生成素-2一样，护骨素与疾病严重程度成比例增加，并与严重程度指标包括肌酐、乳酸、白介素6、内皮细胞黏附分子ICAM-1和E-选择素以及微血管反应性受损独立相关。骨保护素也与一氧化氮依赖的内皮功能障碍独立相关。在那些患有严重诺氏疟疾的人中，88%发现了AKI。血管生成素-2和护骨素均为急性肾损伤的独立危险因素。我们的发现表明，溶血介导的内皮激活和WPB成分的释放可能是严重诺氏疟疾患者包括AKI在内的终末器官功能障碍的关键因素。
Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel–Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.
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影响因子：
3
作者：
Cox-Singh J;Hiu J;Lucas SB;Divis PC;Zulkarnaen M;Chandran P;Wong KT;Adem P;Zaki SR;Singh B;Krishna S
通讯作者：
Krishna S
影响因子：
4.3
作者：
Abu El-Asrar AM;Nawaz MI;Kangave D;Mairaj Siddiquei M;Geboes K
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Geboes K
影响因子：
3
作者：
Herdiana H;Cotter C;Coutrier FN;Zarlinda I;Zelman BW;Tirta YK;Greenhouse B;Gosling RD;Baker P;Whittaker M;Hsiang MS
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Hsiang MS
影响因子：
4.4
作者：
Abu El-Asrar, Ahmed M.;Struyf, Sofie;Simo, Rafael
通讯作者：
Simo, Rafael
影响因子：
11.8
作者：
Barber, Bridget E.;William, Timothy;Yeo, Tsin W.
通讯作者：
Yeo, Tsin W.