Acquisition of Antibodies Against Endothelial Protein C Receptor–Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria

• Published in: The Journal of infectious diseases Vol. 219; no. 5; pp. 808 - 818
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15-02-2019
• Subjects: Antibodies; Children; Erythrocyte membrane protein 1; Erythrocytes; Immunoglobulin G; Malaria; Membrane proteins; Plasmodium falciparum; Protein C; Proteins; Papua New Guinea; severe malaria; antibodies; EPCR; CIDR; Luminex assay; PfEMP1; Plasmodium falciparum
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiy564

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.
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.