Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A
Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A
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DOI：
10.4049/jimmunol.165.6.3309
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发表时间：
2000-09-15
影响因子：
4.4
通讯作者：
Hviid, L
中科院分区：
文献类型：
--
作者：
Ricke, CH;Staalsoe, T;Hviid, L
在恶性疟原虫传播严重的地区，儿童时期就获得了临床免疫力，成年人也享有很大的疟疾保护。这一规则的一个例外是怀孕妇女，她们的疟疾比非怀孕妇女更普遍，也更严重。流行地区的妊娠相关疟疾（PAM）集中在最初的几次妊娠中，表明对PAM的保护性免疫是产次的函数。PAM中胎盘通常被严重感染，并且胎盘寄生虫显示出对硫酸软骨素A（CSA）作为粘附受体的显著偏好，来自暴露于疟疾的经产妇女的血浆Ab能够在体外干扰恶性疟原虫寄生虫与CSA的结合，因此，干扰CSA特异性寄生虫隔离的Ab的获得似乎是获得性抗PAM保护的关键因素。在这里，我们表明，成人从一个地区的高流行性P，恶性疟原虫传播一般具有低水平的抗体特异性识别表面抗原表达的CSA粘附寄生虫分离株，而抗疟原虫分离株得到了很好的认可。与此形成鲜明对比的是，该地区的大多数妊娠晚期孕妇血浆中此类抗体水平非常高。特异性识别CSA粘附分离株的抗体血浆水平强烈依赖于产次，而对CSA非粘附分离株的识别则不依赖于产次。最后，我们证明了一个明确的相关性抗体识别CSA特异性分离物的血浆水平和干扰的能力：与它的螯合CSA在体外。我们的研究支持了这样的假设，即抑制CSA特异性寄生虫隔离的抗体在获得针对PAM的保护中是重要的。
In areas of intense Plasmodium falciparum transmission, clinical immunity is acquired during childhood, and adults enjoy substantial protection against malaria. An exception to this rule is pregnant women, in whom malaria is both more prevalent and severe than in nonpregnant women. Pregnancy-associated malaria (PAM) in endemic areas is concentrated in the first few pregnancies, indicating that protective immunity to PAM is a function of parity, The placenta is often heavily infected in PAM, and placental parasites show a striking preference for chondroitin sulfate A (CSA) as an adhesion receptor, Plasma Abs from malaria-exposed multiparous women are able to interfere with binding of P. falciparum parasites to CSA in vitro, and acquisition of Abs interfering with CSA-specific parasite sequestration thus appears to be a critical element in acquired protection against PAM. Here we show that adults from an area of hyperendemic P, falciparum transmission generally possessed low levels of Abs specifically recognizing surface Ags expressed by a CSA-adhering parasite isolate, while unselected isolates were well recognized. In marked contrast, most third-trimester pregnant women from that area had very high plasma levels of such Abs, Plasma levels of Abs specifically recognizing the CSA-adhering isolate strongly depended on parity, whereas recognition of CSA-nonadhering isolates did not. Finally, we demonstrate a clear correlation between plasma levels of Abs recognizing the CSA-specific isolate and the ability to interfere: with its sequestration to CSA in vitro. Our study supports the hypothesis that Abs inhibiting CSA-specific parasite sequestration are important in acquisition of protection against PAM.