Cox Sharon E, Staalsoe Trine, Arthur Paul, Bulmer Judith N, Hviid Lars, Yeboah-Antwi Kojo, Kirkwood Betty R, Riley Eleanor M
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel St., London, WC1E 7HT, United Kingdom.
Infect Immun. 2005 May;73(5):2841-7. doi: 10.1128/IAI.73.5.2841-2847.2005.
Recent evidence suggests that pregnancy-associated malaria (PAM), associated with maternal anemia and low birth weight, results from preferential sequestration of parasitized red blood cells (pRBC) in the placenta via binding of variant surface antigens (VSA) expressed on the surface of pRBC to chondroitin sulfate A (CSA). The VSA mediating CSA binding (VSA(CSA)) and thus sequestration of pRBC in the placenta are antigenically distinct from those that mediate pRBC sequestration elsewhere in the body, and it has been suggested that VSA(CSA) are relatively conserved and may thus constitute an attractive target for vaccination against PAM. Using flow cytometry, levels of antibody to VSA and VSA(CSA) expressed on the surface of red blood cells infected with Plasmodium falciparum isolates were measured during pregnancy and lactation in Ghanaian primigravid women enrolled in a trial of maternal vitamin A supplementation. Antibody responses to VSA(CSA) were detected within the first trimester of pregnancy and increased with increasing duration of pregnancy, and they seemed to be isolate specific, indicating that different CSA-adherent parasite lines express antigenically distinct VSA and thus may not be as antigenically conserved as has been previously suggested. Levels of anti-VSA(CSA) were not significantly associated with placental malarial infection determined by histology, indicating that primary immune responses to VSA(CSA) may not be sufficient to eradicate placental parasitemia in primigravidae.
近期证据表明,与孕产妇贫血和低出生体重相关的妊娠相关疟疾(PAM),是由于寄生的红细胞(pRBC)表面表达的变异表面抗原(VSA)与硫酸软骨素A(CSA)结合,从而使pRBC优先滞留于胎盘所致。介导CSA结合(VSA(CSA))并因此使pRBC滞留于胎盘的VSA在抗原性上与介导pRBC滞留于身体其他部位的VSA不同,有人提出VSA(CSA)相对保守,因此可能构成抗PAM疫苗的一个有吸引力的靶点。在一项孕产妇补充维生素A试验中,对加纳初孕妇女在妊娠和哺乳期感染恶性疟原虫分离株的红细胞表面表达的VSA和VSA(CSA)抗体水平进行了流式细胞术检测。在妊娠的头三个月内检测到了对VSA(CSA)的抗体反应,且随着妊娠时间的延长而增加,而且这些反应似乎具有分离株特异性,这表明不同的CSA黏附寄生虫株表达抗原性不同的VSA,因此可能不像之前所认为的那样在抗原性上保守。通过组织学确定的抗VSA(CSA)水平与胎盘疟疾感染无显著相关性,这表明对VSA(CSA)的初次免疫反应可能不足以根除初孕妇女的胎盘寄生虫血症。