Acquisition of IgG to ICAM-1-Binding DBLβ Domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 Antigen Family Varies between Groups A, B, and C

Infect Immun. 2019 Sep 19;87(10):e00224-19. doi: 10.1128/IAI.00224-19. Print 2019 Oct.

Abstract

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important malaria virulence factor. The protein family can be divided into clinically relevant subfamilies. ICAM-1-binding group A PfEMP1 proteins also bind endothelial protein C receptor and have been associated with cerebral malaria in children. IgG to these PfEMP1 proteins is acquired later in life than that to group A PfEMP1 not binding ICAM-1. The kinetics of acquisition of IgG to group B and C PfEMP1 proteins binding ICAM-1 is unclear and was studied here. Gene sequences encoding group B and C PfEMP1 with DBLβ domains known to bind ICAM-1 were used to identify additional binders. Levels of IgG specific for DBLβ domains from group A, B, and C PfEMP1 binding or not binding ICAM-1 were measured in plasma from Ghanaian children with or without malaria. Seven new ICAM-1-binding DBLβ domains from group B and C PfEMP1 were identified. Healthy children had higher levels of IgG specific for ICAM-1-binding DBLβ domains from group A than from groups B and C. However, the opposite pattern was found in children with malaria, particularly among young patients. Acquisition of IgG specific for DBLβ domains binding ICAM-1 differs between PfEMP1 groups.

Keywords: PfEMP1; Plasmodium falciparum; antibodies; immunity; malaria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan / biosynthesis*
  • Child
  • Child, Preschool
  • Erythrocytes / immunology
  • Erythrocytes / parasitology
  • Female
  • Gene Expression
  • Ghana
  • Humans
  • Immunoglobulin G / biosynthesis*
  • Infant
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / immunology
  • Malaria, Cerebral / genetics
  • Malaria, Cerebral / immunology*
  • Malaria, Cerebral / parasitology
  • Malaria, Cerebral / pathology
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / pathology
  • Male
  • Plasmodium falciparum / immunology*
  • Plasmodium falciparum / pathogenicity
  • Polymorphism, Genetic
  • Protein Binding
  • Protein Domains
  • Protozoan Proteins / classification
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / immunology
  • Seasons
  • Severity of Illness Index

Substances

  • Antibodies, Protozoan
  • ICAM1 protein, human
  • Immunoglobulin G
  • Protozoan Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Intercellular Adhesion Molecule-1