Fc/R IIA polymorphism -131H/R and malaria severity in Ghanaian children

Abstract

Plasmodium falciparum malaria still remains a major public health problem in most parts of the world especially in Sub Saharan Africa. Pathogenesis of severe malaria is still not fully understood and several factors have been suggested to play a role. Fc receptors constitutes a crucial link between humoral and cellular immune responses and are thought be important in the pathogenesis of severe malaria. Fc RIIA which belongs to the family of Fc receptors are predominantly expressed on neutrophils which have been shown to kill merozoites. Thus variants of Fc RIIA may influence the binding affinity of IgG and subsequently affect phagocytosis and parasite clearance. On the other hand, increased binding affinity and enhanced phagocytosis can also stimulate the release of some immune factors in quantities that are detrimental leading to severe malaria. The objective of this study was to investigate the role of the Fc RIIA-131H/R variant in the pathogenesis of severe malaria in Ghanaian children. Methods: This study was a hospital based unmatched case-control study involving 290 malaria cases and controls. The study was conducted at the Korle-Bu Teaching Hospital in Accra, Ghana. PCR-RFLP was used to characterize the Fc RIIA-131H/R polymorphism in 210 Ghanaian children with uncomplicated malaria, severe malaria anaemia, and cerebral malaria. Results: The study revealed that the 131HH genotype is associated with susceptibility to cerebral malaria (OR = 4.0, 95% CI = 1.28—12.52; p = 0.014). The results also revealed that carriers of the R allele had a significantly lower parasitaemia (p < 0.050) than non-carriers. Conclusion: The presence of Fc RIIA-131HH which is regarded as a low affinity variant may lead to decreased phagocytosis and poor control of parasitaemia in Ghanaian Children. This however does not exclude the possibility that IgG binding to the Fc RIIA-131HH variant can stimulate the release of factors that may contribute to the development cerebral malaria.