Endothelial Gene Expression in Kidney Transplants with Alloantibody Indicates Antibody-Mediated Damage Despite Lack of C4d Staining
Endothelial Gene Expression in Kidney Transplants with Alloantibody Indicates Antibody-Mediated Damage Despite Lack of C4d Staining
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DOI：
10.1111/j.1600-6143.2009.02761.x
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发表时间：
2009-10-01
影响因子：
8.8
通讯作者：
Halloran, Philip F.
中科院分区：
文献类型：
--
作者：
Sis, Banu;Jhangri, Gian S.;Halloran, Philip F.
抗HLA同种异体抗体是移植物丢失的危险因素，但并不表明哪些肾脏正在经历抗体介导的排斥反应（ABMR）。活检组织中的C4d染色对ABMR具有特异性，但不敏感。我们推测，由于同种抗体作用于微循环而引起的内皮基因表达的改变将是ABMR的敏感指标。我们从文献中鉴定了119种内皮相关转录物（ENDATs），并通过微阵列研究了173例肾移植活检标本中它们的表达。平均ENDAT表达在所有排斥反应中均增加，但在ABMR中高于T细胞介导的排斥反应，并与ABMR的组织病理学病变和同种抗体相关。许多个体ENDAT在ABMR中增加，并预测移植物丢失。与对照组相比，具有高ENDAT和抗体的肾脏显示ABMR病变增加和预后更差。只有40%的ENDAT高表达和慢性ABMR或移植物丢失的肾脏被C4d阳性诊断。与C4d相比，抗体的ENDAT高表达预测移植物丢失的灵敏度更高（77% vs. 31%），特异性略低（71% vs. 94%）。结果在82个肾脏的独立组中得到验证。同种抗体患者肾内皮转录本高表达是活性抗体介导的同种异体移植物损伤和移植物预后不良的指标。
Anti-HLA alloantibody is a risk factor for graft loss, but does not indicate which kidneys are experiencing antibody-mediated rejection (ABMR). C4d staining in biopsies is specific for ABMR but insensitive. We hypothesized that altered expression of endothelial genes due to alloantibody acting on the microcirculation would be sensitive indicator of ABMR. We identified 119 endothelial-associated transcripts (ENDATs) from literature, and studied their expression by microarrays in 173 renal allograft biopsies for cause. Mean ENDAT expression was increased in all rejection but was higher in ABMR than in T-cell-mediated rejection and correlated with histopathologic lesions of ABMR, and alloantibody. Many individual ENDATs were increased in ABMR and predicted graft loss. Kidneys with high ENDATs and antibody showed increased lesions of ABMR and worse prognosis in comparison to controls. Only 40% of kidneys with high ENDAT expression and chronic ABMR or graft loss were diagnosed by C4d positivity. High ENDAT expression with antibody predicts graft loss with higher sensitivity (77% vs. 31%) and slightly lower specificity (71% vs. 94%) than C4d. The results were validated in independent set of 82 kidneys. High renal endothelial transcript expression in patients with alloantibody is indicator of active antibody-mediated allograft damage and poor graft outcome.