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Identification of a 'Plasmodium falciparum' Protein Domain that Could Play a Key Role in the Development of Severe Malaria

The study paves the way towards antibody-based interventions that inhibit the interaction between the parasite protein and its human receptor

15.11.2016
Photo: NIH

 A protein expressed at the surface of red blood cells infected by Plasmodium falciparum could be a key player in the vascular pathology that leads to severe malaria by binding to the gC1qR receptor, according to a study led by ISGlobal researchers. The results of the study, published in Plos Pathogens, pave the way towards therapeutic interventions based on antibodies that inhibit this specific interaction.    

Mortality due to severe malaria remains unacceptably high, despite the administration of effective antimalarial drugs. Though the mechanisms underlying life-threatening malaria remain largely unknown and depend both on host and parasite factors, it is known that the sequestration of infected red blood cells (erythrocytes) in vital organs plays a key role. This in turn depends on the adhesion of infected erythrocytes to receptors on the vascular endothelium, a process thought to be mediated by a complex family of parasite proteins expressed at the surface of infected erythrocytes (PfEMP1s).  

In this study, the authors hypothesized that certain PfEMP1s mediate binding to gC1qR, a receptor expressed by a wide range of human cells and previously associated with severe malaria. The results, obtained with more than 80 P falciparum isolates of Mozambican children with or without severe malaria, as well as a parasite line selected in the laboratory, show that a conserved domain in the DC8 variants of the PfEMP1 binds to gC1qR. Furthermore, antibodies against such domain were capable of inhibiting the interaction with gC1qR, regardless of the strain, suggesting the feasibility of designing therapeutic interventions against severe malaria.   

Children under 5 years of age are one of most vulnerable groups affected by malaria. There were an estimated 438 000 malaria deaths worldwide in 2015, of which approximately 69% were in children under 5 years of age.

Reference

Magallón-Tejada A, Machevo S, Cisteró P, et al. Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria. PLoS Pathog. 2016 Nov 11;12(11):e1006011.