Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Front Immunol. 2021 Aug 23;12:724331. doi: 10.3389/fimmu.2021.724331. eCollection 2021.
The functional Fc gamma receptor (FcγR) IIIA polymorphism -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 -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 -V/F158. There was also no independent survival effect in a multivariable Cox model. Similarly, functional polymorphisms in two other activating FcγR, -H/R131 (FcγRIIA) and -NA1/NA2 (FcγRIIIB), 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 FcγR polymorphism with microcirculation inflammation may not be strong enough to exert a meaningful effect on graft survival.
功能 Fc 受体（FcγR）IIIa 多态性 -V/F158 先前被认为决定了供体特异性 HLA 抗体引发微循环炎症的潜力，而微循环炎症是抗体介导的肾移植排斥反应的关键病变。然而，迄今为止，尚未评估其与长期移植结局的关系。为了阐明 -V/F158 多态性对肾移植存活的影响，我们对 1940 对受者/供者对进行了基因分型。分析 10 年无死亡的移植物存活率，我们发现 -V/F158 与之无关。多变量 Cox 模型也没有独立的生存影响。同样，两种其他激活型 FcγR（-H/R131（FcγRIIA）和 -NA1/NA2（FcγRIIIB）的功能性多态性也与结局无关。在易发生与排斥反应相关损伤的患者亚组中，如预致敏受者（> 0% 面板反应性；n = 438）或移植后 1 年内接受排斥反应治疗的受者（n = 229）中，也没有显著的生存差异。我们的研究结果表明，先前显示的 FcγR 多态性与微循环炎症的关联可能不够强，无法对移植物存活产生有意义的影响。
