Red blood cell complement receptor one level varies with Knops blood group, α(+)thalassaemia and age among Kenyan children.

D H Opi,J A Rowe,T N Williams,E N Orori,S Uyoga

doi:10.1038/gene.2016.2

D H Opi, J A Rowe + Show 3 more

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https://doi.org/10.1038/gene.2016.2

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Abstract

Both the invasion of red blood cells (RBCs) by Plasmodium falciparum parasites and the sequestration of parasite-infected RBCs in the microvasculature are mediated in part by complement receptor one (CR1). RBC surface CR1 level can vary between individuals by more than 20-fold and may be associated with the risk of severe malaria. The factors that influence RBC CR1 level variation are poorly understood, particularly in African populations. We studied 3535 child residents of a malaria-endemic region of coastal Kenya and report, for the first time, that the CR1 Knops blood group alleles Sl2 and McCb, and homozygous HbSS are positively associated with RBC CR1 level. Sickle cell trait and ABO blood group did not influence RBC CR1 level. We also confirm the previous observation that α+thalassaemia is associated with reduced RBC CR1 level, possibly due to small RBC volume, and that age-related changes in RBC CR1 expression occur throughout childhood. RBC CR1 level in malaria-endemic African populations is a complex phenotype influenced by multiple factors that should be taken into account in the design and interpretation of future studies on CR1 and malaria susceptibility.

Highlights

Plasmodium falciparum is the most common cause of malaria world wide and is responsible for the vast majority of malaria deaths.[1]
We analysed the relationship between red blood cells (RBCs) CR1 level and age as a continuous variable, using piecewiselinear regression analysis, which allows for adjustment for known confounding variables such as α+thalassaemia.[14]
An increasing body of evidence from in vitro studies supports a role for CR1 in the pathogenesis of severe malaria,[4,5,6,7,8,9] yet little is known about the determinants of RBC CR1 level variation in African populations

Summary

Introduction

Plasmodium falciparum is the most common cause of malaria world wide and is responsible for the vast majority of malaria deaths.[1]. CR1 acts as a receptor on RBCs for both P. falciparum invasion[4,5,6,7] and rosette formation, in which two or more uninfected RBCs bind to a P. falciparum parasitised RBC in vitro.[8,9] Rosetting has been associated with severe malaria in multiple African study sites (reviewed in Rowe et al.10), potentially because it leads to enhanced parasitised RBC sequestration and decreased blood flow in post-capillary venules.[11,12] CR1 acts as a receptor for P. falciparum RBC invasion via its interaction with the parasite ligand P. falciparum reticulocyte-binding-like homologue protein 4.4–7

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