The FcgammaRIIIA-158 VV genotype increased the risk of post-transplant lymphoproliferative disorder in T-cell depleted kidney transplant recipients.

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication in organ transplant recipients. The use of T lymphocyte-depleting antibodies (TLDAb), especially rabbit TLDAb contributes to PTLD and the V158F polymorphism of Fc gamma receptor IIIA (FcgammaRIIIA) also named CD16A could affect the concentration-effect relationship of TLDAb. We therefore investigated the association of this polymorphism with PTLD in kidney transplant recipients. METHODS: We characterized the V158F polymorphism in two case-control cohorts (discovery, n=196; validation, n=222). Then, we evaluated the binding of rabbit IgG to human FcgammaRIIIA-158V and -158F. RESULTS: The V158F polymorphism was not linked to PTLD in the overall cohorts, but risk of PTLD was increased in VV homozygous recipients receiving TLDAb compared to F carriers in both cohorts, especially in recipients receiving TLDAb without muromonab (discovery: HR=2.22 [1.03-4.76], p=0.043, validation: HR=1.75 [1.01-3.13], p=0.049). In vitro, we found that the binding of rabbit IgG to human NK cell FcgammaRIIIA was increased when cells expressed the 158-V versus the 158-F allotype. CONCLUSIONS: While the 158-V allotype of human FcgammaRIIIA binds rabbit immunoglobulin-G with higher affinity, the risk of PTLD was increased in homozygous VV kidney transplant recipients receiving polyclonal TLDAb.