Department of Internal Medicine, Section Nephrology and Transplantation, Na516, Erasmus MC, University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Sci Rep. 2021 Apr 12;11(1):7903. doi: 10.1038/s41598-021-86943-3.
Natural killer (NK) cells express the Fc-gamma 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 3.5 × 10 versus 1.3 × 10 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.
自然杀伤 (NK) 细胞表达 Fc 受体 γ 链 CD16（FCGR3A），因此在慢性活动性抗体介导的排斥反应 (c-aABMR) 中可能介导肾内皮细胞损伤。FCGR3A 158 等位基因 F/V 多态性的 V/V 基因型与 NK 细胞 CD16 表达和细胞毒性增加有关。本研究评估了该基因型是否与 c-aABMR 和肾移植失败的诊断有关。与对照组肾移植受者 (N=116，P=0.65) 相比，c-aABMR 病例 (N=133) 的 FCGR3A 158 F/V 基因型分布无差异。V 等位基因与 NK 细胞 CD16 的中荧光强度 (MFI) 增加相关 (MFI 3.5×10 对 V/V 和 F/F 基因型，P<0.001)。CD16 表达增加与 NK 细胞依赖 CD16 的脱颗粒相关 (R=0.4；P=0.02)。此外，V/V 基因型与更高的肾小球肾炎评分和独立的移植肾存活率降低的危险因素显著相关 (HR 1.98；P=0.04)。c-aABMR 病例在 3 年随访时，FCGR3A 158 基因型的死亡风险调整移植物存活率为 33%，而 F/F 基因型为 62%。总之，FCGR3A V/V 基因型增加了 CD16 介导的 NK 细胞细胞毒性，并与 c-aABMR 病例中更高的肾小球肾炎评分和移植物存活率降低相关。
