Evidence for the involvement of VAR2CSA in pregnancy-associated malaria

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

Research output: Contribution to journalArticlepeer-review

476 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1197-1203
Number of pages7
JournalJournal of Experimental Medicine
Volume200
Issue number9
DOIs
Publication statusPublished - 1 Nov 2004
Externally publishedYes

Keywords

  • PfEMP1
  • Plasmadium falciparum
  • Vaccine
  • Var gene
  • Var2csa

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