肾移植术后高水平BK病毒尿症与HLA位点关联分析

Association analysis of high level of BK virus viruria and HLA site after kidney transplantation

目的探讨肾移植术后高水平BK病毒(BKV)尿症的时间分布, 以及高水平BKV尿症与临床因素以及供、受者特定人类白细胞抗原(HLA)位点的关联。方法回顾性分析于2017年1月1日至2019年12月31日于西安交通大学第一附属医院行器官捐献供肾肾移植的212例受者的资料, 定义肾移植术后尿液BKV-DNA定量大于107(拷贝/ml)尿液为高水平BKV尿症, 选择同期性别组成相同的低于该阈值的212例受者作为低水平对照组。对于两组间临床资料及HLA位点进行统计描述, 使用单因素以及多因素Logistic回归筛选高水平BKV尿症的危险因素。结果肾移植术后受者首次高水平BKV尿症发生时间中位数为125.5 d。在单因素Logistic分析中, 移植肾功能延迟(DGF)以及受者HLA-A24是高水平BKV尿症的危险因素, 供者HLA-DQ9是保护因素。在多因素Logistic分析中, DGF(OR=2.18, 95%CI 1.18~4.01, P=0.012)以及受者HLA-A24(OR=1.63, 95%CI 1.06~2.53, P=0.027)是高水平BKV尿症的独立危险因素, 供者HLA-DQ9(OR=0.58, 95%CI 0.36~0.91, P=0.019)是独立保护因素。结论肾移植术后高水平BKV尿症和供者及受者特定的HLA位点相关, 针对危险因素及保护因素对受者进行早期危险因素分层有助于定制术后免疫抑制剂、筛查方案和开发T淋巴细胞相关疫苗。

Objective To explore the temporal distribution of high level of BK virus(BKV)viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods From January 1,2017 to December 31,2019,clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>107(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions.Results The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis,delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis,DGF(OR=2.18,95%CI 1.18~4.01,P=0.012)and HLA-A24(OR=1.63,95%CI 1.06~2.53,P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors(OR=0.58,95%CI 0.36~0.91,P=0.019)was an independent protective factor.Conclusions High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.