Wellcome Trust Centre for Human Genetics and Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
J Proteome Res. 2013 Mar 1;12(3):1211-22. doi: 10.1021/pr300858g. Epub 2013 Feb 12.
Plasmodium falciparum is a protozoan parasite that causes human malaria. This parasitic infection accounts for approximately 655,000 deaths each year worldwide. Most deaths could be prevented by diagnosing and treating malaria promptly. To date, few parasite proteins have been developed into rapid diagnostic tools. We have combined a shotgun and a targeted proteomic strategy to characterize the plasma proteome of Gambian children with severe malaria (SM), mild malaria, and convalescent controls in search of new candidate biomarkers. Here we report four P. falciparum proteins with a high level of confidence in SM patients, namely, PF10_0121 (hypoxanthine phosphoribosyltransferase, pHPRT), PF11_0208 (phosphoglycerate mutase, pPGM), PF13_0141 (lactate dehydrogenase, pLDH), and PF14_0425 (fructose bisphosphate aldolase, pFBPA). We have optimized selected reaction monitoring (SRM) assays to quantify these proteins in individual patients. All P. falciparum proteins were higher in SM compared with mild cases or control subjects. SRM-based measurements correlated markedly with clinical anemia (low blood hemoglobin concentration), and pLDH and pFBPA were significantly correlated with higher P. falciparum parasitemia. These findings suggest that pHPRT is a promising biomarker to diagnose P. falciparum malaria infection. The diagnostic performance of this marker should be validated prospectively.
疟原虫是一种引起人类疟疾的原生动物寄生虫。这种寄生虫感染每年在全球造成约 65.5 万人死亡。通过及时诊断和治疗疟疾，大多数死亡是可以预防的。迄今为止，只有少数寄生虫蛋白被开发成快速诊断工具。我们结合了一种鸟枪法和靶向蛋白质组学策略，来描述冈比亚患有严重疟疾（SM）、轻度疟疾和恢复期对照儿童的血浆蛋白质组，以寻找新的候选生物标志物。在这里，我们报告了在 SM 患者中具有高置信度的四种疟原虫蛋白，即 PF10_0121（次黄嘌呤磷酸核糖基转移酶，pHPRT）、PF11_0208（磷酸甘油酸变位酶，pPGM）、PF13_0141（乳酸脱氢酶，pLDH）和 PF14_0425（果糖二磷酸醛缩酶，pFBPA）。我们已经优化了选择反应监测（SRM）测定法，以在个体患者中定量这些蛋白质。与轻度病例或对照受试者相比，所有疟原虫蛋白在 SM 中均升高。基于 SRM 的测量值与临床贫血（低血血红蛋白浓度）明显相关，pLDH 和 pFBPA 与更高的疟原虫寄生虫血症显著相关。这些发现表明 pHPRT 是诊断疟原虫疟疾感染的有前途的生物标志物。该标志物的诊断性能应前瞻性验证。
