Evidence for the involvement of VAR2CSA in pregnancy-associated malaria

J Exp Med. 2004 Nov 1;200(9):1197-203. doi: 10.1084/jem.20041579.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa
  • Birth Weight / immunology*
  • Chondroitin Sulfates / metabolism*
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / metabolism
  • Male
  • Microscopy, Confocal
  • Placenta / parasitology*
  • Pregnancy
  • Protozoan Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Sex Factors


  • DNA Primers
  • Immunoglobulin G
  • Protozoan Proteins
  • Recombinant Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Chondroitin Sulfates