In falciparum malaria, sequestration, mediated by Plasmodium falciparum erythrocyte membrane protein1 (PfEMP1) in postcapillary venules is implicated in pathogenesis of severe disease, such as cerebral malaria. Specific PfEMP1 subtypes, more specifically domain cassettes (DC) 8 and 13, which bind to endothelial protein C receptor (EPCR) have been associated with severe malaria. Infected Erythrocytes (IE) bind to EPCR through the cysteine-rich interdomain region (CIDRα) of DC8 and 13. CIDR domains broadly consist of three classes: α, β and γ. The α domains can be further divided based on the type of PfEMP1 being expressed and binding phenotype into Group B and CD36 binding (CIDR α2-6), Group A and EPCR binding (CIDR α1.4-1.7), Group B/A and EPCR binding (CIDR α1.1&1.8). Antibody to different PfEMP1 types develops with exposure, and protects against further infection with that type. In Papua New Guinea (PNG), we investigated whether antibody recognition of different PfEMP1 proteins on admission or in convalescence differed between children with severe malaria, uncomplicated malaria and community controls.
We measured IgG and opsonising antibodies against different parasite lines expressing Group A and non-Group A PfEMP1 and to recombinant PfEMP1s, specifically CIDR α1.1-6 domains. Plasma samples from 112 children from each disease category were tested using Luminex assay for antibodies to 35 recombinant CIDR domains and six control proteins; 1047 samples were tested in a phagocytosis assay to measure opsonising antibodies to four parasite lines.
At presentation, antibody levels were similar across the three groups. In convalescence, older children with severe malaria more frequently showed higher antibody levels to EPCR binding CIDR domains (DC8 and Group A CIDR- EPCR domains) relative to admission, than did children with mild malaria.
This data suggests CIDRα domains may have a role in pathogenesis of severe malaria in PNG children.