TY - JOUR

T1 - Dynamics of PfEMP1 Antibody Profile From Birth to 12 Months of Age in Beninese Infants

AU - Moussiliou, A.

AU - Turner, L.

AU - Cottrell, G.

AU - Doritchamou, J.

AU - Gbédandé, K.

AU - Fievet, N.

AU - Luty, A. J.F.

AU - Massougbodji, A.

AU - Theander, T. G.

AU - Deloron, P.

AU - Lavstsen, T.

AU - Tuikue Ndam, N.

PY - 2020

Y1 - 2020

N2 - BACKGROUND: Plasmodium falciparum-infected erythrocytes bind to specific endothelial cell receptors via members of the PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich interdomain region (CIDR) domains found in the N-terminal region of all PfEMP1. CIDRα1 domains bind endothelial protein C receptor (EPCR), CIDRα2-6 domains bind CD36, whereas the receptor specificity of CIDRβ/γ/δ domains is unknown. METHODS: In this study, we investigated the level of immunoglobulin (Ig)G 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 CIDRα1 domains were more frequent in cord blood compared with antibodies to CIDRα2-6 domains. Higher IgG levels to EPCR-binding CIDRα1 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 6 months of life. At 12 months, children had acquired antibody to all types of CIDR domains, mostly in children with documented P falciparum infections. CONCLUSIONS: 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.

AB - BACKGROUND: Plasmodium falciparum-infected erythrocytes bind to specific endothelial cell receptors via members of the PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich interdomain region (CIDR) domains found in the N-terminal region of all PfEMP1. CIDRα1 domains bind endothelial protein C receptor (EPCR), CIDRα2-6 domains bind CD36, whereas the receptor specificity of CIDRβ/γ/δ domains is unknown. METHODS: In this study, we investigated the level of immunoglobulin (Ig)G 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 CIDRα1 domains were more frequent in cord blood compared with antibodies to CIDRα2-6 domains. Higher IgG levels to EPCR-binding CIDRα1 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 6 months of life. At 12 months, children had acquired antibody to all types of CIDR domains, mostly in children with documented P falciparum infections. CONCLUSIONS: 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.

KW - children

KW - CIDR domains

KW - IgG

KW - malaria

KW - PfEMP1

U2 - 10.1093/infdis/jiaa043

DO - 10.1093/infdis/jiaa043

M3 - Journal article

C2 - 32002541

AN - SCOPUS:85086419703

VL - 221

SP - 2010

EP - 2017

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 12

ER -