FcγRIIA polymorphism as a risk factor for invasive Streptococcus pneumoniae

Polymorphisms of human Fc gamma receptor IIA (FcγRIIA) have been described and shown to be associated with susceptibility to and severity of certain infectious diseases. Invasive Streptococcus pneumoniae infection continues to be a major cause of morbidity and mortality throughout the world and effective host defense against S. pneumoniae depends on immunoglobulin (Ig) G2–mediated phagocytosis of the bacteria by polymorphonuclear leukocytes. One of the major functions of the FcγRIIA receptor is to play a crucial role in the phagocytosis of IgG2-opsonized bacteria because it is the only receptor able to interact with IgG2 immune complexes. The FcγRIIA polymorphism (FcγRIIA-R131 vs. FcγRIIA-H131) determines the capacity of IgG2-mediated phagocytosis via this receptor. Thus, studies that have examined the direct functional role of R131 and H131 in phagocytosis of the opsonized S. pneumoniae by effector cells in clinically relevant patient groups would provide compelling evidence linking this polymorphism with disease. Here we review the role of FcγRIIA polymorphisms as a host-genetic factor influencing S. pneumoniae infection and describe the in vitro and clinical studies that support the importance of this association.