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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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

Cite this

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: Journal of Infectious Diseases. 2019 ; Vol. 219, No. 5. pp. 808-818.
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title = "Acquisition of Antibodies Against Endothelial Protein C Receptor-Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria",
abstract = "BackgroundPlasmodium 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.",
keywords = "PfEMP1, Plasmodium falciparum, severe malaria, antibodies, Papua New Guinea, Luminex assay, CIDR, EPCR, INFECTED ERYTHROCYTES, EPCR-BINDING, EXPRESSION, SURFACE, SEQUENCE, IMMUNITY, PFEMP1, CYTOADHERENCE, PROTECTION, ADHERENCE",
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.}",
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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. / 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.

In: Journal of Infectious Diseases, Vol. 219, No. 5, 01.03.2019, p. 808-818.

Research output: Contribution to journalArticle

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.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - BackgroundPlasmodium 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.

AB - BackgroundPlasmodium 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.

KW - PfEMP1

KW - Plasmodium falciparum

KW - severe malaria

KW - antibodies

KW - Papua New Guinea

KW - Luminex assay

KW - CIDR

KW - EPCR

KW - INFECTED ERYTHROCYTES

KW - EPCR-BINDING

KW - EXPRESSION

KW - SURFACE

KW - SEQUENCE

KW - IMMUNITY

KW - PFEMP1

KW - CYTOADHERENCE

KW - PROTECTION

KW - ADHERENCE

U2 - 10.1093/infdis/jiy564

DO - 10.1093/infdis/jiy564

M3 - Article

VL - 219

SP - 808

EP - 818

JO - Journal Infectious Diseases

JF - Journal Infectious Diseases

SN - 0022-1899

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