title: Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria.
abstract: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical P. falciparum samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation per se and disease severity within these data. This contrasts with the simple hypothesis that P. falciparum isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom george.warimwe@ndm.ox.ac.uk pb642@cam.ac.uk.|Centre for Research in Therapeutic Sciences and Institute for Healthcare Management, Strathmore University, Nairobi, Kenya.
authors.forename: George M
authors.initials: GM
authors.lastname: Warimwe
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.|Department of Biochemistry and Chemistry, Pwani University, Kilifi, Kenya.
authors.forename: Abdirahman I
authors.initials: AI
authors.lastname: Abdi
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Michelle
authors.initials: M
authors.lastname: Muthui
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Gregory
authors.initials: G
authors.lastname: Fegan
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Musyoki
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom george.warimwe@ndm.ox.ac.uk pb642@cam.ac.uk.|Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Bull
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004912:Erythrocytes / Q000469:parasitology*; D015870:Gene Expression; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum