Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Parasites Causing Cerebral Falciparum Malaria Bind Multiple Endothelial Receptors and Express EPCR and ICAM-1-Binding PfEMP1

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Pulmonary Arterial Enlargement in Well-Treated Persons With Human Immunodeficiency Virus

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A Systematic Review of Clinical Practice Guidelines for the Diagnosis and Management of Bronchiolitis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Biomarkers for Disease Severity in Children Infected With Respiratory Syncytial Virus: A Systematic Literature Review

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Meta-analysis of Plasmodium falciparum var Signatures Contributing to Severe Malaria in African Children and Indian Adults

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the binding and accumulation of infected erythrocytes (IE) to blood vessels and tissues. Specific interactions have been described between PfEMP1 and human endothelial proteins CD36, intercellular adhesion molecule-1 (ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediatric malaria syndromes and the associated PfEMP1 members are still undefined.

Methods: In a cohort of 94 hospitalized children with malaria, we characterized the binding properties of IE collected on admission, and var gene transcription using quantitative polymerase chain reaction.

Results: IE from patients with cerebral malaria were more likely to bind EPCR and ICAM-1 than IE from children with uncomplicated malaria (P = .007). The level of transcripts encoding CIDRα1.4 and CIDRα1.5 domain subclasses was higher in patients with severe disease (P < .05). IE populations exhibiting binding to all 3 receptors had higher levels of transcripts encoding PfEMP1 with CIDRα1.4 and Duffy binding-like (DBL)-β3 domains than parasites, which only bound CD36.

Conclusions: These results underpin the significance of EPCR binding in pediatric malaria patients that require hospital admission, and support the notion that complementary receptor interactions of EPCR binding PfEMP1with ICAM-1 amplifies development of severe malaria symptoms.

Original languageEnglish
JournalThe Journal of infectious diseases
Volume215
Issue number12
Pages (from-to)1918-1925
Number of pages8
ISSN0022-1899
DOIs
Publication statusPublished - 15 Jun 2017

    Research areas

  • Antigens, CD, Cell Adhesion, Child, Preschool, Endothelial Cells, Endothelial Protein C Receptor, Humans, Infant, Intercellular Adhesion Molecule-1, Malaria, Cerebral, Malaria, Falciparum, Plasmodium falciparum, Protein Binding, Protozoan Proteins, Receptors, Cell Surface, Transcription, Genetic, Journal Article

ID: 52821937