Ali Salanti 1 , 2 , Madeleine Dahlbäck 1 , 2 , Louise Turner 1 , 2 , Morten A. Nielsen 1 , 2 , Lea Barfod 1 , 2 , Pamela Magistrado 1 , 2 , Anja T.R. Jensen 1 , 2 , Thomas Lavstsen 1 , 2 , Michael F. Ofori 2 , 3 , Kevin Marsh 4 , Lars Hviid 1 , 2 , Thor G. Theander 1 , 2
1 November 2004
In Plasmodium falciparum–endemic areas, pregnancy-associated malaria (PAM) is an important health problem. The condition is precipitated by accumulation of parasite-infected erythrocytes (IEs) in the placenta, and this process is mediated by parasite-encoded variant surface antigens (VSA) binding to chondroitin sulfate A (CSA). Parasites causing PAM express unique VSA types, VSA PAM, which can be serologically classified as sex specific and parity dependent. It is sex specific because men from malaria-endemic areas do not develop VSA PAM antibodies; it is parity dependent because women acquire anti-VSA PAM immunoglobulin (Ig) G as a function of parity. Previously, it was shown that transcription of var2csa is up-regulated in placental parasites and parasites selected for CSA binding. Here, we show the following: (a) that VAR2CSA is expressed on the surface of CSA-selected IEs; (b) that VAR2CSA is recognized by endemic plasma in a sex-specific and parity-dependent manner; (c) that high anti-VAR2CSA IgG levels can be found in pregnant women from both West and East Africa; and (d) that women with high plasma levels of anti-VAR2CSA IgG give birth to markedly heavier babies and have a much lower risk of delivering low birth weight children than women with low levels.