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


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
15 02 2019
Historique:
received: 16 06 2018
accepted: 18 09 2018
pubmed: 27 10 2018
medline: 13 11 2019
entrez: 27 10 2018
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 30365003
pii: 5106640
doi: 10.1093/infdis/jiy564
doi:

Substances chimiques

Antibodies, Protozoan 0
Endothelial Protein C Receptor 0
Immunoglobulin G 0
PROCR protein, human 0
Protozoan Proteins 0
erythrocyte membrane protein 1, Plasmodium falciparum 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

808-818

Informations de copyright

© 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.

Auteurs

Janavi S Rambhatla (JS)

Department of Medicine, The Peter Doherty Institute for Infection and Immunity, Parkville.

Louise Turner (L)

Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Denmark.

Laurens Manning (L)

School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Research Institute, Fiona Stanley Hospital, Murdoch.

Moses Laman (M)

Papua New Guinea Institute of Medical Research, Madang.

Timothy M E Davis (TME)

School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Research Institute, Fiona Stanley Hospital, Murdoch.

James G Beeson (JG)

Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.

Ivo Mueller (I)

Department of Medical Biology, University of Melbourne, Parkville.
Walter and Eliza Hall Institute of Medical Research, Parkville.
Parasite and Insect Vectors Department, Institut Pasteur, Paris, France.

Jonathan Warrel (J)

Papua New Guinea Institute of Medical Research, Madang.

Thor G Theander (TG)

Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Denmark.

Thomas Lavstsen (T)

Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Denmark.

Stephen J Rogerson (SJ)

Department of Medicine, The Peter Doherty Institute for Infection and Immunity, Parkville.

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