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

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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. / Acquisition of Antibodies Against Endothelial Protein C Receptor-Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria. In: The Journal of infectious diseases. 2019 ; Vol. 219, No. 5. pp. 808-818.

Bibtex

@article{0d3da9885d054f1eb477a4d33f8304ad,
title = "Acquisition of Antibodies Against Endothelial Protein C Receptor-Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria",
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.",
keywords = "Antibodies, Protozoan/blood, Child, Child, Preschool, Endothelial Protein C Receptor/metabolism, Female, Humans, Immunoglobulin G/blood, Infant, Infant, Newborn, Malaria, Falciparum/immunology, Male, Papua New Guinea, Plasmodium falciparum/immunology, Protozoan Proteins/immunology",
author = "Rambhatla, {Janavi S} and Louise Turner and Laurens Manning and Moses Laman and Davis, {Timothy M E} and Beeson, {James G} and Ivo Mueller and Jonathan Warrel and Theander, {Thor G} and Thomas Lavstsen and Rogerson, {Stephen J}",
note = "{\circledC} The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",
year = "2019",
month = "2",
day = "15",
doi = "10.1093/infdis/jiy564",
language = "English",
volume = "219",
pages = "808--818",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "University of Chicago Press",
number = "5",

}

RIS

TY - JOUR

T1 - Acquisition of Antibodies Against Endothelial Protein C Receptor-Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria

AU - Rambhatla, Janavi S

AU - Turner, Louise

AU - Manning, Laurens

AU - Laman, Moses

AU - Davis, Timothy M E

AU - Beeson, James G

AU - Mueller, Ivo

AU - Warrel, Jonathan

AU - Theander, Thor G

AU - Lavstsen, Thomas

AU - Rogerson, Stephen J

N1 - © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2019/2/15

Y1 - 2019/2/15

N2 - 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.

AB - 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.

KW - Antibodies, Protozoan/blood

KW - Child

KW - Child, Preschool

KW - Endothelial Protein C Receptor/metabolism

KW - Female

KW - Humans

KW - Immunoglobulin G/blood

KW - Infant

KW - Infant, Newborn

KW - Malaria, Falciparum/immunology

KW - Male

KW - Papua New Guinea

KW - Plasmodium falciparum/immunology

KW - Protozoan Proteins/immunology

U2 - 10.1093/infdis/jiy564

DO - 10.1093/infdis/jiy564

M3 - Journal article

VL - 219

SP - 808

EP - 818

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 5

ER -

ID: 59421488