Dynamics of PfEMP1 antibody profile from birth to 12 months of age in Beninese infants

INTRODUCTION: Plasmodium falciparum infected erythrocytes bind to specific endothelial cell receptors via members of PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich inter-domain region (CIDR) domains found in the N-terminal region of all PfEMP1. CIDRalpha1 domains bind EPCR, CIDRalpha2-6 domains bind CD36 whilst the receptor specificity of CIDRbeta/gamma/delta domains is unknown. METHODS: Here, we investigated the level of IgG targeting the different types of PfEMP1 CIDR during the first year of life. We used plasma collected longitudinally from children of pregnant women who had been followed closely through pregnancy. RESULTS: Antibodies to CIDRalpha1 domains were more frequent in cord blood compared to antibodies to CIDRalpha2-6 domains. Higher IgG levels to EPCR-binding CIDRalpha1 variants positively correlated with the timing of first infections. Antibodies to all PfEMP1 types declined at similar rates to the point of disappearance over the first six months of life. At 12 months, children had acquired antibody to all types of CIDR domains, mostly in children with documented P. falciparum infections. CONCLUSION: These observations agree with the notion that the timing and phenotype of first P. falciparum infections in life are influenced by the immune status of the mother.