title: IgG antibodies to endothelial protein C receptor-binding cysteine-rich interdomain region domains of Plasmodium falciparum erythrocyte membrane protein 1 are acquired early in life in individuals exposed to malaria.
abstract: Severe malaria syndromes are precipitated by Plasmodium falciparum parasites binding to endothelial receptors on the vascular lining. This binding is mediated by members of the highly variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. We have previously identified a subset of PfEMP1 proteins associated with severe malaria and found that the receptor for these PfEMP1 variants is endothelial protein C receptor (EPCR). The binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDR) of the subtypes α1.1 and α1.4 to α1.8. In this study, we investigated the acquisition of anti-CIDR antibodies using plasma samples collected in four study villages with different malaria transmission intensities in northeastern Tanzania during a period with a decline in malaria transmission. We show that individuals exposed to high levels of malaria transmission acquire antibodies to EPCR-binding CIDR domains early in life and that these antibodies are acquired more rapidly than antibodies to other CIDR domains. The rate by which antibodies to EPCR-binding CIDR domains are acquired in populations in areas where malaria is endemic is determined by the malaria transmission intensity, and on a population level, the antibodies are rapidly lost if transmission is interrupted. This indicates that sustained exposure is required to maintain the production of the antibodies.
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark lturner@sund.ku.dk.
authors.forename: Louise
authors.initials: L
authors.lastname: Turner
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavstsen
authors.affiliation: National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania.
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Mmbando
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Magistrado
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lasse S
authors.initials: LS
authors.lastname: Vestergaard
authors.affiliation: National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania.
authors.forename: Deus S
authors.initials: DS
authors.lastname: Ishengoma
authors.affiliation: National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania.
authors.forename: Daniel T R
authors.initials: DT
authors.lastname: Minja
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania.
authors.forename: John P
authors.initials: JP
authors.lastname: Lusingu
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D000074283:Endothelial Protein C Receptor; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D013636:Tanzania; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D007074:Immunoglobulin G; C478370:PROCR protein, human; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C085731:erythrocyte membrane protein 1, Plasmodium falciparum