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首页> 外文期刊>Infection and immunity >High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission
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High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

机译：居住在恶性疟原虫高传播地区的喀麦隆妇女中，针对多个域和VAR2CSA株的高水平抗体与胎盘疟疾缺乏相关。

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Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.
机译：胎盘疟疾是由恶性疟原虫感染的胎盘中的螯合螯合引起的，与产妇发病风险增加和分娩结果差有关。寄生虫抗原VAR2CSA（变异表面抗原2-硫酸软骨素A）在感染的红细胞上表达，并介导与硫酸软骨素A的结合，引发炎症并破坏母胎界面的稳态。尽管抗体可以防止螯合，但是尚不清楚寄生虫清除是由于针对单个Duffy结合样（DBL）域的抗体还是由于针对多个DBL域和等位基因变体的广泛抗体库引起的。因此，从孕妇的纵向采集的血浆样品中筛选了针对广泛的VAR2CSA蛋白的自然获得的抗体，这些蛋白包括5个不同DBL域中每个域的2至3个等位基因变体。对从怀孕3到9个月的喀麦隆高疟和低疟疾传播地区妇女的血浆样本进行了分析。结果表明，从妊娠中期至足月出现抗体时，针对多个VAR2CSA域而不是单个域的高抗体水平与胎盘疟疾的缺失相关。胎盘疟疾的缺乏与多重女性中针对不同DBL域和等位基因变异的抗体广度增加有关。此外，与高传播位点相比，低传播位点的女性的抗体反应具有较低的幅度和较小的广度。这些数据表明，对多个VAR2CSA结构域和等位基因变体的抗体水平高，对胎盘疟疾具有免疫力，并且抗体的广度受疟疾传播强度的影响。

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