Medical Sciences Postgraduation Program, Department of Clinical Medicine, Faculty of Medicine of the Federal University of Ceará, Monsenhor Furtado St, s/n, Fortaleza, CE, 60430-275, Brazil.
ARGOS Patologia, 5753 Santos Dumont av, Room 1604, Office Tower, Fortaleza, Ceará, 60175047, Brazil.
Clin Exp Nephrol. 2021 Mar;25(3):305-314. doi: 10.1007/s10157-020-01994-6. Epub 2020 Nov 26.
There are only a few reports evaluating the applicability of endothelial-damage markers analysis by immunohistochemistry (IHC) in kidney allograft samples. This study analyzed the expression of Caveolin-1 (Cav), von Willebrand factor (Vwf), and T-cadherin (Cad) in kidney biopsies and their association with antibody-mediated injury.
In this retrospective study, 114 cases with antibody-mediated changes (Banff, 2020) and 72 with interstitial fibrosis/tubular atrophy were selected. IHC for Cav, Vwf and Cad was performed and evaluated according to their qualitative expression in peritubular capillaries. The cases were grouped according to the presence of microvascular inflammation (MVI), donor-specific antibodies (DSA), C4d positivity and antibody-mediated rejection (AMR). A level of significance < 0.05 was adopted.
Vwf expression was associated with MVI (p < 0.001), DSA (p = 0.016), C4d (p < 0.001) and AMR (p < 0.001), and was higher in DSA+/C4d+ cases despite MVI (p < 0.001). The expression of Cad correlated with MVI (p = 0.015), C4d (p = 0.005) and AMR (p = < 0.001). Cad was more expressed in chronic AMR compared with acute/active cases (p = 0.001). Cav expression was associated with MVI (p = 0.029) and AMR (p = 0.016) and was also higher in chronic AMR (p = 0.049). A combined score of Vwf and Cad was higher in AMR when compared with C4d without rejection and IF/TA cases (p < 0.001).
Vwf, Cad and Cav expression shows association with antibody-mediated injury and may be helpful to support AMR diagnosis.
仅有少数研究评估了免疫组织化学(IHC)分析血管内皮损伤标志物在肾移植样本中的适用性。本研究分析了 Cav-1(Cav)、血管性血友病因子(Vwf)和 T-钙黏蛋白(Cad)在肾活检组织中的表达及其与抗体介导的损伤的关系。
本回顾性研究纳入了 114 例具有抗体介导改变(Banff,2020)和 72 例间质纤维化/肾小管萎缩的病例。通过 IHC 检测 Cav、Vwf 和 Cad 在肾小管周围毛细血管中的定性表达,并进行评估。根据微血管炎症(MVI)、供体特异性抗体(DSA)、C4d 阳性和抗体介导的排斥反应(AMR)的存在对病例进行分组。采用 P<0.05 为差异有统计学意义。
Vwf 的表达与 MVI(p<0.001)、DSA(p=0.016)、C4d(p<0.001)和 AMR(p<0.001)相关,且在 MVI 存在的情况下,DSA+/C4d+病例的 Vwf 表达更高(p<0.001)。Cad 的表达与 MVI(p=0.015)、C4d(p=0.005)和 AMR(p<0.001)相关。与急性/活跃性 AMR 相比,慢性 AMR 中 Cad 的表达更高(p=0.001)。Cav 的表达与 MVI(p=0.029)和 AMR(p=0.016)相关,在慢性 AMR 中表达更高(p=0.049)。与 C4d 无排斥和 IF/TA 病例相比,Vwf 和 Cad 联合评分在 AMR 中更高(p<0.001)。
Vwf、Cad 和 Cav 的表达与抗体介导的损伤有关,可能有助于支持 AMR 的诊断。