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

Janavi S. Rambhatla, Louise Turner, Laurens Manning, Moses Laman, Timothy M. E. Davis, James G. Beeson, Ivo Mueller, Jonathan Warrel, Thor G. Theander, Thomas Lavstsen, Stephen J. Rogerson

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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 CIDR1 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 CIDR1 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.

Original languageEnglish
Pages (from-to)808-818
Number of pages11
JournalJournal of Infectious Diseases
Volume219
Issue number5
DOIs
Publication statusPublished - 1 Mar 2019

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