Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria

• DOI: 10.1084/jem.20041579
• Publication Date: 2004-11-02T16:52:52Z
• Authors: Ali Salanti; Madeleine Dahlbäck; Louise Turner; Morten A. Nielsen; Lea Barfod; Pamela Magistrado; Anja T.R. Jensen; Thomas Lavstsen; Michael F. Ofori; Kevin Marsh; Lars Hviid; Thor G. Theander
• Keywords: Male; 0303 health sciences; Erythrocytes; Microscopy, Confocal; Placenta; Chondroitin Sulfates; Brief Definitive Report; Protozoan Proteins; Enzyme-Linked Immunosorbent Assay; Recombinant Proteins; 3. Good health; 03 medical and health sciences; Sex Factors; Pregnancy; Immunoglobulin G; Africa; Birth Weight; Humans; Female; Malaria, Falciparum; DNA Primers

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, VSAPAM, which can be serologically classified as sex specific and parity dependent. It is sex specific because men from malaria-endemic areas do not develop VSAPAM antibodies; it is parity dependent because women acquire anti-VSAPAM 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.