title: Evidence for the involvement of VAR2CSA in pregnancy-associated malaria.
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.
authors.affiliation: Centre for Medical Parasitology, Dept. of Medical Microbiology and Immunology, Panum Institute 24-2, Blegdamsvej 3, 2200 Copenhagen, Denmark. salanti@cmp.dk.
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.forename: Madeleine
authors.initials: M
authors.lastname: Dahlbäck
authors.forename: Louise
authors.initials: L
authors.lastname: Turner
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.forename: Lea
authors.initials: L
authors.lastname: Barfod
authors.forename: Pamela
authors.initials: P
authors.lastname: Magistrado
authors.forename: Anja T R
authors.initials: AT
authors.lastname: Jensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavstsen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ofori
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Lars
authors.initials: L
authors.lastname: Hviid
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
mesh_terms: D000349:Africa; D001724:Birth Weight / Q000276:immunology*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D010920:Placenta / Q000469:parasitology*; D011247:Pregnancy; D015800:Protozoan Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012737:Sex Factors
chemical_list: D017931:DNA Primers; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D002809:Chondroitin Sulfates