The Journal of Experimental Medicine
ThymUS '08
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Published 1 November 2004. doi:10.1084/jem.20041579
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 9, 1197-1203
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Brief Definitive Report

 Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria

Ali Salanti1,2, Madeleine Dahlbäck1,2, Louise Turner1,2, Morten A. Nielsen1,2, Lea Barfod1,2, Pamela Magistrado1,2, Anja T.R. Jensen1,2, Thomas Lavstsen1,2, Michael F. Ofori2,3, Kevin Marsh4, Lars Hviid1,2, and Thor G. Theander1,2

1 Centre for Medical Parasitology, Department of Medical Microbiology and Immunology, University of Copenhagen
2 Department of Infectious Diseases, Copenhagen University Hospital, 2200 Copenhagen, Denmark
3 Noguchi Memorial Institute for Medical Research, University of Ghana, 80108 Legon, Ghana
4 Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast Kilifi, Kenya

Address correspondence to Ali Salanti, Centre for Medical Parasitology, Dept. of Medical Microbiology and Immunology, Panum Institute 24-2, Blegdamsvej 3, 2200 Copenhagen, Denmark. Phone: 45-35-32-76-76; Fax: 45-35-32-78-51; email: salanti{at}cmp.dk

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.

Key Words: var gene • var2csa • Plasmodium falciparum • PfEMP1 • vaccine


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