The FCGR3A 158 V/V-Genotype is Associated With Decreased Survival of Renal Allografts With Chronic Active Antibody-Mediated Rejection

Natural killer (NK) cells express the Fc-receptor CD16 ( FCGR3A ) and could therefore mediate renal endothelial cell damage in cases of chronic-active antibody mediated rejection (c-aABMR). The V/V-genotype of the FCGR3A 158 F/V polymorphism is associated with increased CD16 expression and cytotoxicity by NK cells. This study evaluated whether this genotype is associated with the diagnosis of c-aABMR and renal allograft loss.The distribution of the FGCR3A 158 F/V-genotypes was not different for c-aABMR cases (N=133) compared to control kidney transplant recipients (N=116, p=0.65). The V-allele was associated with increased median fluorescence intensity (MFI) of CD16 by NK cells (MFI 3.5x10 4 versus 1.3x10 4 for V/V and F/F-genotype, P<0.001). Increased expression of CD16 correlated with CD16-dependent degranulation of NK cells (R=0.4; P=0.02). Moreover, the V/V-genotype was significantly associated with a higher glomerulitis score and an independent risk factor (HR 1.98; P=0.04) for decreased allograft survival. Death-censored graft survival in c-aABMR cases at 3 years follow-up was 33% for the FCGR3A 158 V/V-genotype versus 62% for the F/F-genotype. In conclusion, the FCGR3A V/V-genotype increases CD16-mediated NK cell cytotoxicity and is associated with a higher glomerulitis score and decreased graft survival in cases with c-aABMR.