Evidence for the involvement of VAR2CSA in pregnancy-associated malaria

TY - JOUR

T1 - Evidence for the involvement of VAR2CSA in pregnancy-associated malaria

AU - Salanti, Ali

AU - Dahlbäck, Madeleine

AU - Turner, Louise

AU - Nielsen, Morten A

AU - Barfod, Lea

AU - Magistrado, Pamela

AU - Jensen, Anja T R

AU - Lavstsen, Thomas

AU - Ofori, Michael F

AU - Marsh, Kevin

AU - Hviid, Lars

AU - Theander, Thor G

N1 - Keywords: Africa; Birth Weight; Chondroitin Sulfates; DNA Primers; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Female; Humans; Immunoglobulin G; Malaria, Falciparum; Male; Microscopy, Confocal; Placenta; Pregnancy; Protozoan Proteins; Recombinant Proteins; Sex Factors

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20041579

DO - 10.1084/jem.20041579

M3 - Journal article

C2 - 15520249

SN - 0022-1007

VL - 200

SP - 1197

EP - 1203

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 9

ER -