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.

Rebecca W. Olsen,Lars Hviid,Anja T. R. Jensen,Anja Bengtsson,Kwadwo A. Kusi,Kwadwo A. Koram,Yvonne Adams,Michael F. Ofori,Gertrude Ecklu-Mensah,John H. Adams

doi:10.1128/iai.00224-19

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.

Highlights

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important malaria virulence factor
Domains downstream of the intercellular adhesion molecule 1 (ICAM-1)-binding DBL␤ domains belonged to groups and subgroups similar to those in the previously identified ICAM-1-binding group B and C PfEMP1 proteins (Fig. 1C)
P. falciparum causes the most severe form of malaria and is responsible for the vast majority of malaria-related deaths [28]. This is not least due to the presence in this species of the PfEMP1 family of adhesive proteins, which are expressed on the surface of infected erythrocytes (IEs) in a mutually exclusive manner [4]

Summary

Introduction

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important malaria virulence factor. Levels of IgG specific for DBL␤ 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. Acquisition of IgG specific for DBL␤ domains binding ICAM-1 differs between PfEMP1 groups. The protection is mediated to a considerable extent by IgG specific for members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, expressed on the surface of infected erythrocytes (IEs) (reviewed in reference 1). Protective immunity to severe malaria is acquired before immunity to uncomplicated disease and asymptomatic infection [10, 11], and this is paralleled by acquisition of group A PfEMP1-specific IgG early in life [12, 13]. The aim was to provide increased understanding of how antibody-mediated immunity to PfEMP1 is acquired following natural exposure to P. falciparum

Methods

Results

Conclusion