Variable adhesion abilities and overlapping antigenic properties in placental Plasmodium falciparum isolates

Abstract

Background: Pregnancy-associated malaria is characterized by selection and multiplication, in the placenta, of a distinct population of Plasmodium falciparum expressing particular variant surface antigens (VSAs) that adhere to chondroitin sulfate A (CSA).

Methods: The adhesion of 40 freshly collected placental parasite isolates to bovine CSA and human placental low-sulfated chondroitin proteoglycans (CSPGs) was investigated. Plasma samples from 30 pregnant women were used to test, by flow cytometry, their recognition of and their adhesion-inhibition capacity toward 6 of these isolates.

Results: Adhesion to CSA and CSPGs varied between isolates but was strongly correlated between receptors (P<.001). Adhesion of isolates to receptors strongly and negatively correlated with low birth weight (LBW) of the neonate (odds ratio [95% confidence interval], 5.2 [1.1-25.1]). In plasma samples from pregnant women, the level of specific immunoglobulin G against each placental isolate (anti-VSA(PAP)) strongly correlated with the level of anti-VSA(PAP) antibodies against all other isolates (P<.05) and increased with parity in all isolates (P<.01). Conversely, adhesion-inhibitory antibodies did not correlate with isolates or with the level of anti-VSA(PAP) antibodies.

Conclusion: The level of adhesion of placental parasites to chondroitin sulfate receptors is an important risk factor for LBW. Parasite heterogeneity suggests that they are composed of mixed adhesion phenotypes capable of inducing immune responses to a range of different and overlapping targets.