Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function
Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function
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DOI：
10.1038/sj.ki.5002795
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发表时间：
2008-04-01
影响因子：
19.6
通讯作者：
Manfro, R. C.
中科院分区：
文献类型：
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作者：
Aquino-Dias, E. C.;Joelsons, G.;Manfro, R. C.
移植肾功能延迟(DGF)常发生在已故供者的肾移植中。我们希望为急性排斥反应(AR)提供更准确的非侵入性测试。利用实时荧光定量聚合酶链式反应检测穿孔素、颗粒酶B、Fas-配体和丝氨酸蛋白酶抑制物-9等细胞溶解分子的表达。我们还测量了FOXP3的表达，FOXP3是已知参与AR的T调节细胞的特征基因。这些研究对35例DGF患者的外周血单核细胞、尿液细胞和48例监测肾活检进行。在这些患者中，20例经组织病理学诊断为AR，而另外28例具有急性肾小管坏死(ATN)的特征。AR患者的活检组织、外周血白细胞和尿细胞中细胞溶解和凋亡相关基因的表达显著高于ATN患者。与FOXP3基因表达相关的诊断参数在外周血白细胞和尿液细胞中的敏感性、特异性、阳性预测值和阴性预测值最准确，准确性在94%到100%之间。我们的研究表明，对患有DGF的肾移植患者外周血白细胞和尿细胞中的特定基因进行定量，可能会为AR提供有用和准确的非侵入性诊断。
Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.