title: Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria.
abstract: BACKGROUND
  Pregnancy-associated malaria caused by Plasmodium falciparum adherence to chondroitin sulfate A in the placental intervillous space is a major cause of low birthweight and maternal anaemia in areas of endemic P falciparum transmission. Adhesion-blocking antibodies that specifically recognise parasite-encoded variant surface antigens (VSA) are associated with resistance to pregnancy-associated malaria. We looked for a possible relation between VSA-specific antibody concentrations, placental infection, and protection from low birthweight and maternal anaemia.
  
  
  METHODS
  We used flow cytometry to measure VSA-specific IgG concentrations in plasma samples taken during child birth from 477 Kenyan women selected from a cohort of 910 women on the basis of HIV-1 status, gravidity, and placental histology. We measured VSA expressed by one placental P falciparum isolate and two isolates selected or not selected for chondroitin sulfate A adhesiveness in-vitro.
  
  
  RESULTS
  Concentrations of plasma IgG specific for VSA, expressed by chondroitin sulfate A-adhering parasites (VSA in pregnancy-associated malaria or vsa-pam), increased with gravidity and were associated with placental histological findings. Women with chronic pregnancy-associated malaria and low or absent VSA-PAM-specific IgG had lower haemoglobin values (reduced by 17 g/L; 95% CI 8.1-25.2) and delivered smaller babies (birthweight reduced by 0.26 kg; 0.10-0.55) than did corresponding women with high VSA-PAM-specific IgG. No such relation was shown for concentrations of IgG with specificity for non-pregnancy-associated malaria VSA.
  
  
  CONCLUSIONS
  VSA-PAM-specific IgG protects against low birthweight and maternal anaemia. Our data indicate an important mechanism of clinical protection against malaria and raise hope for the clinical effectiveness of a potential VSA-based vaccine against pregnancy-associated malaria.
authors.affiliation: Centre for Medical Parasitology at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet) and Institute for Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Staalsoe
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Shulman
authors.forename: Judith N
authors.initials: JN
authors.lastname: Bulmer
authors.forename: Ken
authors.initials: K
authors.lastname: Kawuondo
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Lars
authors.initials: L
authors.lastname: Hviid
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002809:Chondroitin Sulfates / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007230:Infant, Low Birth Weight / Q000276:immunology; D007231:Infant, Newborn; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000276:immunology*; D010922:Placenta Diseases / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000276:immunology* / Q000469:parasitology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D002809:Chondroitin Sulfates