title: Low antibody levels to pregnancy-specific malaria antigens and heightened cytokine responses associated with severe malaria in pregnancy.
abstract: BACKGROUND
  Pregnant women living in unstable malaria transmission settings may develop severe malaria (SM). The pathogenesis of SM in pregnancy is poorly understood.
  
  
  METHODS
  To determine whether SM in pregnancy is associated with lower malarial antibody responses and higher cytokine responses, plasma samples were collected from 121 Sudanese pregnant women of whom 39 were diagnosed with SM. Antibodies to pregnancy-specific and non-pregnancy-specific Plasmodium falciparum variant surface antigens (VSA) and concentrations of cytokines TNF, IFNγ, IL-1β, IL-6, IL-8 and IL-10 were measured.
  
  
  RESULTS
  Pregnant women with SM demonstrated significantly lower antibody levels to pregnancy-specific VSA (P = .020) and higher plasma IFNγ (P = .020), IL-10 (P = .0002) and IL-6 levels (P < .0001) than uninfected pregnant women. Concentrations of inflammatory cytokines IL-1β (P = .001), IL-6 (P = .004) and IL-8 (P = .020) were inversely correlated with antibodies to VAR2CSA-DBL5 in pregnant women with SM. Lower haemoglobin levels and higher parasite densities were associated with lack of pregnancy-specific antibodies (P = .028) and higher levels of inflammatory cytokines, in particular IL-6 and IL-8.
  
  
  CONCLUSIONS
  Pregnant women with SM lack pregnancy-specific malaria immunity, and this correlates with heightened inflammatory cytokine concentrations, low haemoglobin levels and high parasite density, suggesting that failure of antibody to control parasitaemia may contribute to SM pathogenesis.
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne Victoria 3052, Australia.
authors.forename: Upeksha P
authors.initials: UP
authors.lastname: Chandrasiri
authors.forename: Louise M
authors.initials: LM
authors.lastname: Randall
authors.forename: Alfarazdeg A
authors.initials: AA
authors.lastname: Saad
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Bashir
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: Ishag
authors.initials: I
authors.lastname: Adam
mesh_terms: D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D018512:Parasitemia / Q000097:blood / Q000453:epidemiology / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D013397:Sudan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D006454:Hemoglobins
keywords: Plasmodium falciparum infection; Severe malaria; Sudan; VAR2CSA-DBL5; cerebral malaria; cytokines; parasitaemia; pregnancy-specific malaria antigens; severe anaemia; variant surface antigens