title: Antibodies to variant surface antigens of Plasmodium falciparum-infected erythrocytes are associated with protection from treatment failure and the development of anemia in pregnancy.
abstract: BACKGROUND
  In pregnancy-associated malaria (PAM), Plasmodium falciparum-infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonize IEs for phagocytic clearance, helping to prevent maternal anemia and low birth weight in infants.
  
  
  METHODS
  Using serum samples from 141 pregnant Malawian women with parasitemia enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantified levels of immunoglobulin (Ig) G to VSA-PAM by flow cytometry and levels of opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes.
  
  
  RESULTS
  After controlling for gravidity and antimalarial treatment, higher levels of IgG to VSA-PAM were associated with decreased anemia at delivery (odds ratio [OR], 0.66 [95% confidence interval {CI}, 0.46-0.93]; P = .018) and were weakly associated with decreased parasitological failure (OR, 0.78 [95% CI, 0.60-1.03]; P = .075), especially reinfection (OR, 0.73 [95% CI, 0.53-1.01]; P = .057). Higher levels of opsonizing antibodies to CS2 IEs were associated with less maternal anemia (OR, 0.31 [95% CI, 0.13-0.74]; P = .008) and treatment failure (OR, 0.48 [95% CI, 0.25-0.90]; P = .023), primarily because of recrudescent infection (OR, 0.49 [95% CI, 0.21-1.12]; P = .089).
  
  
  CONCLUSIONS
  Higher levels of both IgG antibodies to VSA-PAM and opsonizing antibodies, a functional measure of immunity, correlate with parasite clearance and less anemia in pregnancy malaria.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Gaoqian
authors.initials: G
authors.lastname: Feng
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Aitken
authors.forename: Francisca
authors.initials: F
authors.lastname: Yosaatmadja
authors.forename: Linda
authors.initials: L
authors.lastname: Kalilani
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Anthony
authors.initials: A
authors.lastname: Jaworowski
authors.forename: Julie A
authors.initials: JA
authors.lastname: Simpson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000150:complications*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D000962:Antimalarials / Q000627:therapeutic use; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D008295:Malawi / Q000453:epidemiology; D008562:Membrane Glycoproteins / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000962:Antimalarials; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins