Polymorphism of the Fcγ receptor IIA and malaria morbidity

Fc receptors (FcRs) are expressed on the surface of all types of cells of the immune system. They bind the Fc portion of immunoglobulin (Ig), thereby bridging specific antigen recognition by antibodies with cellular effector mechanisms. FcγRIIA, one of the three receptors for human IgG, is a low-affinity receptor for monomeric IgG, but binds IgG immune complexes efficiently. FcγRIIA is believed to play a major role in eliciting monocyte- and macrophage-mediated effector responses against blood-stage malaria parasites. A G → A single nucleotide polymorphism, which causes an arginine (R) to be replaced with histidine (H) at position 131, defines two allotypes which difer in their avidity for complexed human IgG(2) and IgG(3). Because FcγRIIA-H131 is the only FcγR allotype which interacts efficiently with human IgG(2,) this polymorphism may determine whether parasite-specific IgG(2) may or may not elicit cooperation with cellular imune responses during blood-stage malaria infection. Here, we review data from four published case-control studies describing associations between FcγRIIA R/H131 polymorphism and malaria-related outcomes and discuss possible reasons for some incongruities found in these available results.