A field guide to human Fc-gamma receptors Genetics , cellular expression and interaction with immunoglobulins

Background: Inadequate responses to platelet transfusions, i.e. platelet transfusion refractoriness (PLT refractoriness), are a serious problem in the supportive care to thrombocytopenic patients. Multiple factors contribute to low yields upon platelet transfusion, among which are platelet-reactive alloantibodies. Platelet-reactive allo-antibodies occur in up to 30% of patients receiving multiple transfusions, and presumably lead to rapid destruction of the transfused platelets via receptors for IgG, the Fc-gamma receptors (FcγRs), on effector phagocytes. Genetic variation in FcγRs is associated with susceptibility to immune thrombocytopenia (ITP), in which auto-antibodies against platelets cause thrombocytopenia. We hypothesized that genetic variation in FcγRs may also influence PLT refractoriness in allo-immunized patients, and could help in identifying the patients at risk. Study design and methods: Patients with severe PLT refractoriness for whom diagnostic testing for allo-immunization was requested in the period of 2005 – 2013 were retrospectively included. A case-control study was performed comparing patients in whom platelet-reactive antibodies were detected (n=222) with healthy controls (n=210), to determine differences in all known functional copy number variations and single nucleotide polymorphisms in FcγRs. Results: After correction for possible ethnic differences between the group of allo-immunized patients with severe PLT refractoriness and the healthy controls, none of the tested FcγR genetic variations seemed associated with the development of severe PLT refractoriness. Conclusion: In contrast to the situation in ITP, genetic variation in FcγRs does not influence the chance to develop PLT refractoriness. Determination of FcγR genetic background is not useful in identifying the patients most at risk for PLT refractoriness.