ntibody monitoring and graft biopsy after renal transplantation contribute to early diagnosis of antibody mediated rejection
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摘要:
目的 分析肾移植术后抗人类白细胞抗原(HLA)抗体监测和移植肾穿刺病理学检查早期诊断抗体介导的排斥反应(AMR)的必要性。 方法 筛选51例术后产生新生供体特异性抗体(dnDSA)的受者，检测供体特异性抗体(DSA)及其结合C1q的能力，同时进行移植肾穿刺病理诊断。对于符合AMR诊断的受者，比较分析移植肾功能不稳定组和稳定组受者的DSA类别、补体结合能力和移植肾病理组织Banff评分。对无排斥反应组、移植肾功能不稳定组和稳定组受者的移植物进行Kalan-Meier生存分析。 结果 在移植肾功能不稳定组和稳定组受者中，HLA抗体的不同类别、DSA的平均荧光强度(MFI)值、补体相关检测C1q结合力和C4d管周毛细血管沉积情况差异均无统计学意义(均为P＞0.05)。在组织形态学损伤方面，两组在微血管炎、动脉内膜炎、肾小管-间质炎、移植肾小球病、肾小管萎缩-间质纤维化等表现的Banff评分差异均无统计学意义(均为P＞0.05)。移植肾功能不稳定组受者移植物累积存活率显著低于稳定组，稳定组明显低于不符合排斥病理诊断的受者(P=0.002)。 结论 肾移植术后定期监测抗HLA抗体和做移植肾病理穿刺检查非常必要，有助于早期发现和诊断AMR。 Abstract:Objective To analyze the necessity of anti-human leukocyte antigen (HLA) antibody monitoring and graft biopsy on early diagnosis of antibody-mediated rejection (AMR). Methods Fifty-one recipients with de novo donor specific antibody (dnDSA) were screened and chosen. Donor specific antibody (DSA) and its ability to bind with C1q were evaluated. Pathological biopsy of the kidney graft was performed. The recipients diagnosed with AMR were divided into the unstable and stable kidney function groups. Type of DSA, binding ability of the complement and Banff score were statistically compared between two groups. Kaplan-Meier survival analysis of the kidney graft in the recipients from non-rejection, unstable and stable kidney function groups was performed. Results Type of HLA antibody, mean fluorescent intensity (MFI) of DSA, C1q binding ability and C4d deposition in peritubular capillary did not significantly differ between the unstable and stable groups (all P>0.05). Histomorphologically, the Banff score of microvasculitis, endarteritis, renal tubule-interstitial nephritis, transplantation glomerulopathy and renal tubular atrophy-stroma fibrosis did not significantly differ between two groups (all P>0.05). In the unstable group, the accumulated survival rate of the kidney graft was significantly lower compared with that in the stable group, which was significantly lower than that of their counterparts who were ineligible for pathological diagnosis (P=0.002). Conclusions It is necessary to perform regular anti-HLA antibody monitoring and pathological puncture examination after renal transplantation, which contributes to early detection and diagnosis of AMR. -
Key words:
- Renal transplantation /
- Antibody mediated rejection /
- Donor-specific antibody /
- Biopsy
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图 1 3组受者移植肾的Kaplan Meier生存曲线
Figure 1. Kaplan Meier survival curves for kidney graft of recipients in 3 groups
表 1 AMR受者移植肾功能不稳定组与稳定组的临床和病理特点
Table 1. Clinical and pathological features of AMR recipients with stable and unstable function
指 标 移植肾功能不稳定组(n=15) 移植肾功能稳定组(n=30) P值 年龄(岁) 41±13 35±13 0.202 性别(男/女，n/n) 8/7 22/8 0.077 供者类型(亲属活体/尸体，n/n) 4/11 8/22 0.458 移植后时间[年，M(Q1/4～3/4)] 7.0(1.0,12.7) 4.5(1.6,7.0) 0.656 DSA Ⅰ类(n) 6 7 0.56 DSA Ⅱ类(n) 14 30 0.33 C1q-DSA(n) 9 18 0.629 dnDSA MFI(x±s) 12 545±5 255 11 021±4 830 0.338 肾穿检查时Scr(μmol/L，x±s) 363±134 143±39 0.000 肾穿检查时24 h尿蛋白[g，M(Q1/4～3/4)] 2.0(0.5,5.1) 0.5(0.2,1.0) 0.014 Banff评分[M(Q1/4～3/4)] 小球炎+管周毛细血管炎 3(3,3) 3(2.5,3.5) 0.958 C4d管周毛细血管沉积 2.0(1.0,3.0) 2.0(0.5,3.0) 0.664 移植肾小球病 1.0(0,3.0) 0(0,1.0) 0.436 肾小管-间质炎 2.0(1.0,2.0) 1.0(0,3.0) 0.140 动脉内膜炎 0(0,1.0) 0(0,0) 0.617 肾小管萎缩-间质纤维化 1.0(1.0,2.0) 1.0(1.0,1.5) 0.292 注：DSA为供体特异性抗体；dnDSA为新生供体特异性抗体；MFI为平均荧光强度；Scr为血清肌酐 
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