Development of antibodies against chondroitin sulfate A-adherent Plasmodium falciparum in pregnant women

In areas where Plasmodium falciparum is endemic, pregnant women are at incr eased risk for malaria, and this risk is greatest during the first pregnanc y. The placenta sequesters parasites that are able to cytoadhere to chondro itin sulfate A (CSA), a molecule expressed by the placental syncytiotrophob last, while parasites from a nonpregnant host do not bind to CSA. Cytoadher ence is mediated by the expression of variants of the P. falciparum-erythro cyte membrane protein 1 family. Each member of this molecule family induces antibodies that specifically agglutinate infected erythrocytes and inhibit their cytoadherence ability. We investigated whether the higher susceptibi lity of primigravidae was related to the lack of immune response towards CS A-binding parasites. In a cross-sectional study, primigravidae delivering w ith a noninfected placenta were less likely to have antibodies agglutinatin g CSA-binding parasites than multigravidae (P < 0.01). In contrast, parasit es from nonpregnant hosts were as likely to be recognized by the sera from women of various parities. In a longitudinal study, at 6 months of pregnanc y, antibodies against CSA-binding parasites were present in 31.8% of primig ravidae and in 76.9% of secundigravidae (P = 0.02). The antibodies against CSA-binding parasites inhibited the cytoadherence of a CSA-adherent parasit e strain to the human placental trophoblast. Our data support the idea that the higher susceptibility of primiparae is related to a lack of a specific immune response to placental parasites.