Kenya Medical Research Institute-Wellcome Trust Research Programme, P. O. Box 230-80108 Kilifi, Kenya.
Sci Transl Med. 2012 Apr 11;4(129):129ra45. doi: 10.1126/scitranslmed.3003247.
PfEMP1 is a family of cytoadhesive surface antigens expressed on erythrocytes infected with Plasmodium falciparum, the parasite that causes the most severe form of malaria. These surface antigens play a role in immune evasion and are thought to contribute to the pathogenesis of the malaria parasite. Previous studies have suggested a role for a specific subset of PfEMP1 called "group A" in severe malaria. To explore the role of group A PfEMP1 in disease, we measured the expression of the var genes that encode them in parasites from clinical isolates collected from children suffering from malaria. We also looked at the ability of these clinical isolates to induce rosetting of erythrocytes, which indicates a cytoadhesion phenotype that is thought to be important in pathogenesis. These two sets of data were correlated with the presence of two life-threatening manifestations of severe malaria in the children: impaired consciousness and respiratory distress. Using regression analysis, we show that marked rosetting was associated with respiratory distress, whereas elevated expression of group A-like var genes without elevated rosetting was associated with impaired consciousness. The results suggest that manifestations of malarial disease may reflect the distribution of cytoadhesion phenotypes expressed by the infecting parasite population.
PfEMP1 是一种在感染疟原虫（引起最严重疟疾的寄生虫）的红细胞表面表达的细胞黏附表面抗原家族。这些表面抗原在免疫逃避中发挥作用，被认为有助于疟原虫的发病机制。先前的研究表明，一组称为“组 A”的特定 PfEMP1 亚群在严重疟疾中发挥作用。为了探索组 A PfEMP1 在疾病中的作用，我们测量了从患有疟疾的儿童临床分离株中采集的寄生虫中编码它们的 var 基因的表达。我们还观察了这些临床分离株诱导红细胞形成缗钱状的能力，这表明一种细胞黏附表型，被认为在发病机制中很重要。这两组数据与儿童中两种危及生命的严重疟疾表现相关：意识障碍和呼吸窘迫。使用回归分析，我们表明明显的缗钱状与呼吸窘迫相关，而无明显缗钱状但组 A 样 var 基因表达升高与意识障碍相关。结果表明，疟疾疾病的表现可能反映了感染寄生虫群体表达的细胞黏附表型的分布。
