title: Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.
abstract: BACKGROUND
  Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria.
  
  
  METHODS
  Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.
  
  
  RESULTS
  Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria.
  
  
  CONCLUSIONS
  These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. mduffy@unimelb.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Duffy
authors.affiliation: The Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Rintis
authors.initials: R
authors.lastname: Noviyanti
authors.affiliation: Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: The Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Leily
authors.initials: L
authors.lastname: Trianty
authors.affiliation: The Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Boni F
authors.initials: BF
authors.lastname: Sebayang
authors.affiliation: Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Eizo
authors.initials: E
authors.lastname: Takashima
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Fransisca
authors.initials: F
authors.lastname: Sumardy
authors.affiliation: Timika Malaria Research Program, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lampah
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Turner
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavstsen
authors.affiliation: The Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Freya J I
authors.initials: FJ
authors.lastname: Fowkes
authors.affiliation: The Papua New Guinea Institute for Medical Research, Madang, Papua New Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Jutta
authors.initials: J
authors.lastname: Marfurt
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: The Nossal Institute for Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Graham V
authors.initials: GV
authors.lastname: Brown
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.|Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007214:Indonesia; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D015800:Protozoan Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum
keywords: PfEMP1; Severe malaria; var genes