肾移植术后非HLA抗体的特征性移植肾病理表现与表达分析  

Analysis of characteristic pathological manifestations and expressions of non-HLA antibodies after kidney transplantation

作　　者：黄照茹 刘磊[1] 丰翼 王军祥[1] 闫勇闯 王志刚[1] 谢红昌[1] 齐元博 李金锋[1] 尚文俊[1] Huang Zhaoru;Liu Lei;Feng Yi;Wang Junxiang;Yan Yongchuang;Wang Zhigang;Xie Hongchang;Qi Yuanbo;Li Jinfeng;Shang Wenjun(First Affiliated Hospital,Zhengzhou University,Henan 450000,China)

机构地区：[1]郑州大学第一附属医院肾移植科,郑州450000

出　　处：《中华器官移植杂志》2024年第10期710-717,共8页Chinese Journal of Organ Transplantation

基　　金：河南省高等学校重点科研项目计划(23A320002)。

摘　　要：目的分析肾移植术后非HLA抗体特征性移植肾病理表现,并探讨不同病理表现时非HLA抗体的差异。方法回顾性分析2021年2月至2023年6月郑州大学第一附属医院因不明原因血清肌酐升高而接受病理穿刺的同时行HLA抗体检测、检测结果为非HLA抗体阳性且HLA抗体阴性或HLA抗体阳性被判定为供者特异性抗体(donor specific antibody,DSA)且平均荧光强度(mean fluorescence intensity,MFI)>4000的肾移植受者。根据非HLA抗体和HLA抗体检测结果将受者分为单纯非HLA抗体阳性组(45例)和HLA-DSA阳性组(28例)。采用Luminex单抗原微珠法检测抗体。采用χ^(2)检验、t检验或Mann-Whitney U非参数检验两组受者的病理表现进行差异性分析,并根据差异分析结果将单纯非HLA抗体阳性组受者分为微血管炎性组(22例)和非微血管炎性组(23例)、间质纤维化组(36例)和非间质纤维化组(9例),将非HLA抗体水平进行标准化,采用R语言Complex-Heatmap包生成热图,用秩和检验对病理表现不同的非HLA抗体水平进行差异性分析。结果单纯非HLA抗体阳性组和HLA-DSA阳性组受者的微血管炎症阳性率分别为48.9%(22/45)和82.1%(23/28),组间差异有统计学意义(χ^(2)=8.073,P=0.006);两组受者间质纤维化阳性率分别为80.8%(36/45)和53.6%(15/28),组间差异有统计学意义(χ^(2)=5.726,P=0.021)。单纯非HLA抗体阳性组受者中,微血管炎症组的抗蛛毒素受体1、角蛋白8、角蛋白18、干燥综合征抗原B的抗体的相对水平高于非微血管炎症组,差异有统计学意义[559.50(262.00,801.25)比285.00(183.00,460.00),P=0.024;504.50(369.5,725.25)比317.00(231.50,458.00),P=0.014;672.50(454.50,969.50)比399.00(246.50,772.50),P=0.030;967.50(482.00,2066.50)比399.00(246.50,772.50),P=0.033]。间质纤维化组的抗环瓜氨酸肽、集落刺激因子2、细胞间黏附分子1、胶原蛋白Ⅳ抗体的相对水平高于非间质纤维化组,差异有统计学意义[100.00(79.88,167.50)比64.ObjectiveTo explore the characteristic pathological manifestations of non-HLA antibodies after kidney transplantation(KT)and examine the differences of MFT values of non-HLA antibodies in different pathological manifestations.MethodsThe study was conducted on KT recipients at the First Affiliated Hospital of Zhengzhou University from February 2021 to June 2023 with unexplained elevated serum creatinine.Patients undergoing pathological puncture and concurrent HLA antibody testing were included,focusing on those with DSA(MFI>4000)and non-HLA antibody negativity.According to the detection results of non-HLA and HLA antibodies,they were assigned into two groups of non-HLA antibody positive(45 cases)and HLA-DSA positive(28 cases).Both non-HLA and HLA antibodies were detected by luminex single antigen microbeads,χ^(2),t or Mann-Whitney U nonparametric tests were utilized for examining the inter-group differences in pathological manifestations.The recipients with positive non-HLA antibodies were grouped according to the differential pathological features[microvascular inflammation group(22 cases)and non-microvascular inflammation group(23 cases),interstitial fibrosis group(39 cases)and non-interstitial fibrosis(9 cases)].MFI values of non-HLA antibodies were standardized and heat map was generated with R language ComplexHeatmap package.The differences of response values of non-HLA antibodies with different pathological manifestations were examined by rank-sum test.ResultsThe positive rates of microvascular inflammation were 48.9%(22/45)and 82.1%(23/28)in HLA-DSA positive and non-HLA antibody positive groups with statistical significance(χ^(2)=8.073,P=0.006).The positive rates of interstitial fibrosis in two groups were 80.8%(36/45)and 53.6%(15/28)and the difference was statistically significant(χ^(2)=5.726,P=0.021).The relative levels of anti-arachnotoxin receptor 1(Latrophilin 1,LPHN1),keratin 8(KRT8),keratin 18(KRT18)and Sjogren's syndrome antigen B(SSB)were higher in microvascular inflammation group than those in

关 键 词：肾移植 非人组织相容性抗体 供者特异性抗体 肾脏病理 

分 类 号：R699.2[医药卫生—泌尿科学]