Bachmann Julie, Burté Florence, Pramana Setia, Conte Ianina, Brown Biobele J, Orimadegun Adebola E, Ajetunmobi Wasiu A, Afolabi Nathaniel K, Akinkunmi Francis, Omokhodion Samuel, Akinbami Felix O, Shokunbi Wuraola A, Kampf Caroline, Pawitan Yudi, Uhlén Mathias, Sodeinde Olugbemiro, Schwenk Jochen M, Wahlgren Mats, Fernandez-Reyes Delmiro, Nilsson Peter
SciLifeLab Stockholm, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
Division of Parasitology, Medical Research Council National Institute for Medical Research, London, United Kingdom.
PLoS Pathog. 2014 Apr 17;10(4):e1004038. doi: 10.1371/journal.ppat.1004038. eCollection 2014 Apr.
Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.
全身炎症反应以及被寄生红细胞的隔离是儿童重症恶性疟原虫疟疾病理生理学的核心过程。然而,目前仍不清楚为何有些儿童比其他儿童更容易出现疟疾并发症。为了鉴定血浆中与儿童疟疾综合征相关的人类蛋白质,采用了多重抗体悬浮微珠阵列技术。在对700多名儿童血浆中分析的1015种蛋白质中,41种在疟疾感染儿童和社区对照之间存在差异,而13种能够区分非重症疟疾和重症疟疾综合征。发现氧化应激标志物与重症疟疾贫血有关,而内皮激活、血小板黏附和肌肉损伤标志物则与脑型疟疾患儿有关。这些发现表明,重症疟疾存在全身性血管炎症、血管壁调节、内皮激活以及葡萄糖代谢失衡。血浆中特定肌肉蛋白水平升高表明在脑型疟疾病程中可能存在肌肉损伤和微血管病变。