Burnet Institute for Medical Research and Public Health, Melbourne.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville.
J Infect Dis. 2019 Feb 15;219(5):819-828. doi: 10.1093/infdis/jiy580.
Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited.
Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity.
Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria.
Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.
疟原虫感染的红细胞（IEs）在微血管中的隔离导致儿童严重疟疾的发病机制。这种机制是由 IE 表面表达的抗原介导的。然而，对于针对严重疟疾具有保护作用的 IE 表面抗原抗体的具体靶点和功能的了解是有限的。
在巴布亚新几内亚的幼儿中进行了一项与严重或非复杂性疟疾相关的病例对照研究（n = 448），使用与严重疟疾相关的具有毒力表型的分离物和功能调理吞噬测定法，检查 IE 表面抗原的抗体。我们使用遗传修饰的分离物和重组疟原虫红细胞膜蛋白 1（PfEMP1）结构域来定量 PfEMP1 作为与疾病严重程度相关的抗体的靶标。
IE 表面和重组 PfEMP1 结构域的抗体在非复杂性疟疾与严重疟疾之间存在显著差异，并且在感染后会增加。使用遗传修饰的疟原虫表明 PfEMP1 是抗体的主要靶标，并且 PfEMP1 特异性抗体与严重疟疾的发生几率降低有关。此外，单核细胞调理吞噬 IE 的抗体在严重疟疾患者中较低。
这些发现表明 PfEMP1 是与严重疟疾风险降低相关的抗体的主要靶标，并通过促进调理吞噬作用起作用。
