肾移植术后非HLA抗体与体液性排斥反应相关性研究

Correlation between post-transplant non-HLA antibodies and humoral rejection after kidney transplantation

目的探讨术后非人类白细胞抗原(HLA)抗体与肾移植体液性排斥反应(HR)的相关性。方法回顾性分析上海交通大学医学院附属仁济医院2019年9月至2021年1月检测了非HLA抗体水平的40例肾移植受者资料, 选取活检证实发生HR, 并且发生HR时供者特异性HLA抗体阴性或者弱阳的受者入组HR组(11例), 选取术后2周至检测非HLA抗体时移植肾功能稳定的受者入组稳定组(29例)。采用Luminex单抗原微珠法检测HLA抗体、MHCⅠ类链相关基因A(MICA)抗体、32种非HLA抗体的水平, 采用酶联免疫吸附试验(ELISA)检测血管紧张素Ⅱ1型受体(AT1R)抗体水平。分析两组受者非HLA抗体阳性率和阳性非HLA抗体数量的差异。结果 24例受者具有阳性非HLA抗体, 剩余16例受者的非HLA抗体全为阴性。HR组分别有3例受者的肌动蛋白(ACTIN)抗体、Ⅲ型胶原蛋白(Collagen Ⅲ)抗体、谷胱甘肽硫转移酶θ1(GSTT1)抗体和γ干扰素(IFN-γ)抗体阳性, 而稳定受者的这4种非HLA抗体都是阴性, 两组比较, 差异有统计学意义(P=0.017)。4例HR受者的Collagen Ⅱ抗体阳性, 而仅1例稳定受者的Collagen Ⅱ抗体阳性, HR受者的Collagen Ⅱ抗体阳性率高于稳定受者(P=0.023)。HR受者的平均阳性非HLA抗体数为2.36个, 而稳定受者为0.90个, 两组之间的差异有统计学意义(P=0.008)。结论高水平非HLA抗体增加肾移植HR的发生风险。

Objective To explore the correlation between post-transplant non-HLA antibodies and humoral rejection(HR)after kidney transplantation(KT).Methods A retrospective study was conducted for KT recipients with non-HLA antibody level detected from September 2019 to January 2021.The recipients with biopsy confirmed HR and donor-specific HLA antibodies negative or feeble positive at the time of HR were designated as HR group while recipients with stable renal allograft function from 2 weeks post-KT to the time of detecting non-HLA antibody as stable group.The levels of HLA antibody,MHC classⅠchain-related gene A(MICA)antibody and 32 non-HLA antibodies were tested by Luminex single antigen bead and the levels of angiotensinⅡtype 1 receptor(AT1R)antibody quantified by enzyme-linked immunosorbent assay(ELISA).Inter-group differences in positive rate of non-HLA antibodies and number of positive non-HLA antibodies were analyzed.Results Twenty-four recipients had positive non-HLA antibodies while the remainders had no positive non-HLA antibodies.Three HR recipients were positive for actin antibody,collagenⅢantibody,glutathione S-transferase theta-1 antibody or IFN-γantibody respectively.However,all four non-HLA antibodies of stable recipients were negative.There was significant inter-group difference(P=0.017).Four HR recipients were positive for collagenⅡantibody while only 1 stable recipient was positive for collagenⅡantibody.The positive rate of collagenⅡantibody was significantly higher in HR recipients than that in stable recipients(P=0.023).HR recipients had an average of 2.36 positive non-HLA antibodies while stable recipients had an average of 0.90.There was significant inter-group difference(P=0.008).Conclusions A high level of non-HLA antibodies may elevate the risk of HR after KT.