Acquisition of Antibodies Against Endothelial Protein C Receptor–Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria. (26th October 2018)

• Record Type: Journal Article
• Authors: Rambhatla, Janavi S; Turner, Louise; Manning, Laurens; Laman, Moses; Davis, Timothy M E; Beeson, James G; Mueller, Ivo; Warrel, Jonathan; Theander, Thor G; Lavstsen, Thomas; Rogerson, Stephen J
• Is Part Of: Journal of infectious diseases. Volume 219:Number 5(2019)
• Page Start: 808
• Page End: 818
• Publication Date: 2018-10-26
• Subjects: PfEMP1 -- Plasmodium falciparum -- severe malaria -- antibodies -- Papua New Guinea -- Luminex assay -- CIDR -- EPCR; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy564
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite sequestration in postcapillary venules in P. falciparum malaria. PfEMP1 types can be classified based on their cysteine-rich interdomain region (CIDR) domains. Antibodies to different PfEMP1 types develop gradually after repeated infections as children age, and antibodies to specific CIDR types may confer protection. Methods: Levels of immunoglobulin G to 35 recombinant CIDR domains were measured by means of Luminex assay in acute-stage (baseline) and convalescent-stage plasma samples from Papua New Guinean children with severe or uncomplicated malaria and in healthy age-matched community controls. Results: At baseline, antibody levels were similar across the 3 groups. After infection, children with severe malaria had higher antibody levels than those with uncomplicated malaria against the endothelial protein C receptor (EPCR) binding CIDRα1 domains, and this difference was largely confined to older children. Antibodies to EPCR-binding domains increased from presentation to follow-up in severe malaria, but not in uncomplicated malaria. Conclusions: The acquisition of antibodies against EPCR-binding CIDRα1 domains of PfEMP1 after a severe malaria episode suggest that EPCR-binding PfEMP1 may have a role in the pathogenesis of severe malaria in Papua New Guinea. Abstract : Papua New Guinean children with severe malaria acquired antibodies against Endothelial Protein C Receptor-binding domains of Plasmodium falciparum erythrocyte membrane protein 1 during convalescence. Antibody levels increased from clinical presentation to convalescence only in older children with severe malaria.