Functional Fc Gamma Receptor Gene Polymorphisms and Long-Term Kidney Allograft Survival

The functional Fc gamma receptor (Fc gamma R) IIIA polymorphism FCGR3A-V/F158 was earlier suggested to determine the potential of donor-specific HLA antibodies to trigger microcirculation inflammation, a key lesion of antibody-mediated renal allograft rejection. Associations with long-term transplant outcomes, however, have not been evaluated to date. To clarify the impact of FCGR3A-V/F158 polymorphism on kidney transplant survival, we genotyped a cohort of 1,940 recipient/donor pairs. Analyzing 10-year death-censored allograft survival, we found no significant differences in relation to FCGR3A-V/F158. There was also no independent survival effect in a multivariable Cox model. Similarly, functional polymorphisms in two other activating Fc gamma R, FCGR2A-H/R131 (Fc gamma RIIA) and FCGR3B-NA1/NA2 (Fc gamma RIIIB), were not associated with outcome. There were also no significant survival differences among patient subgroups at increased risk of rejection-related injury, such as pre-sensitized recipients (> 0% panel reactivity; n = 438) or recipients treated for rejection within the first year after transplantation (n = 229). Our study results suggest that the earlier shown association of Fc gamma R polymorphism with microcirculation inflammation may not be strong enough to exert a meaningful effect on graft survival.

Automated summary

The FCGR3A-V/F158 polymorphism was not significantly associated with kidney transplant survival, nor were other activating Fc gamma receptor polymorphisms. There were no significant survival differences among patient subgroups at increased risk of rejection-related injury.