Brook N R, White S A, Waller J R, Bicknell G R, Nicholson M L
Division of Transplant Surgery, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
Br J Surg. 2003 Aug;90(8):1009-14. doi: 10.1002/bjs.4133.
Acute allograft rejection is thought to be a risk factor for chronic allograft nephropathy, the cardinal features of which are vasculopathy, interstitial fibrosis and glomerulosclerosis. Fibrosis-associated genes might act as ad interim surrogate markers for chronic allograft nephropathy. The aim of this study was to determine mRNA expression of fibrosis-associated genes in glomeruli plucked from protocol renal transplant biopsies, in patients with or without a history of acute rejection.
A consecutive series of 52 patients (31 male, 21 female) was assessed. Donor categories were cadaveric, living related or asystolic. Transplant recipients received either cyclosporin- or tacrolimus-based immunosuppression. Patients routinely underwent percutaneous needle-core renal transplant biopsy at 1 week, and 3 and 6 months. Acute rejection episodes were confirmed histologically and treated with intravenous methylprednisolone, or antithymocyte globulin if steroid resistant. Individual glomeruli were plucked and total mRNA was extracted. Fibrosis-associated genes were amplified by reverse transcriptase-polymerase chain reaction (PCR) and quantified by enzyme-linked immunosorbent assay.
The expression of both collagen type III (mean 0.42 versus 0.31 arbitrary units of PCR products corrected for a housekeeping gene) and collagen IV (mean 0.46 versus 0.42 arbitrary units) at 6 months did not differ between recipients who experienced acute rejection episodes and those who were free from rejection. There was also no significant difference between groups in terms of mRNA expression of collagen IValpha2, matrix metalloproteinase 2, tissue inhibitor of matrix metalloproteinases 1 and 2, transforming growth factor beta or tenascin.
These results suggest that acute rejection episodes do not increase the expression of fibrosis-associated genes in glomeruli from renal transplant biopsies.
急性移植物排斥反应被认为是慢性移植物肾病的一个危险因素，其主要特征是血管病变、间质纤维化和肾小球硬化。纤维化相关基因可能作为慢性移植物肾病的临时替代标志物。本研究的目的是确定在有或无急性排斥反应病史的患者中，从方案肾移植活检中摘取的肾小球中纤维化相关基因的mRNA表达情况。
对连续的52例患者（31例男性，21例女性）进行评估。供体类别为尸体供体、亲属活体供体或心脏停搏供体。移植受者接受基于环孢素或他克莫司的免疫抑制治疗。患者在术后1周、3个月和6个月常规接受经皮针芯肾移植活检。急性排斥反应发作通过组织学确诊，对类固醇抵抗者用静脉注射甲基泼尼松龙或抗胸腺细胞球蛋白治疗。摘取单个肾小球并提取总mRNA。通过逆转录聚合酶链反应（PCR）扩增纤维化相关基因，并通过酶联免疫吸附测定进行定量。
在6个月时，经历急性排斥反应发作的受者与未发生排斥反应的受者相比，III型胶原蛋白（校正管家基因后PCR产物的平均任意单位为0.42对0.31）和IV型胶原蛋白（平均任意单位为0.46对0.42）的表达没有差异。在I型胶原蛋白α2、基质金属蛋白酶2、基质金属蛋白酶组织抑制剂1和2、转化生长因子β或腱生蛋白的mRNA表达方面，两组之间也没有显著差异。
这些结果表明，急性排斥反应发作不会增加肾移植活检肾小球中纤维化相关基因的表达。
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