Coupes B M, Newstead C G, Short C D, Brenchley P E
Department of Renal Medicine, Manchester Royal Infirmary, United Kingdom.
Transplantation. 1994 Jun 27;57(12):1727-31.
Transforming growth factor beta (TGF beta 1) is a prosclerotic cytokine implicated in several disease processes. Recent reports have demonstrated a role for TGF beta 1 in experimental models of glomerulonephritis, focusing attention on the relevance of TGF beta to renal fibrogenesis in human disease. The study reported here was designed to investigate whether circulating, active TGF beta 1 could be detected in renal allograft recipients, and whether plasma levels correlated with episodes of rejection, a process involving both inflammation and fibrosis. We have developed an ELISA assay for active TGF beta 1 using commercially available antibodies, and measured plasma levels in 43 healthy controls, 11 patients with membranous nephropathy (MN) and impaired renal function, 17 transplant recipients with stable renal function, 27 patients with acute cellular rejection, 7 patients with chronic vascular rejection, and 10 patients with acute tubular necrosis and/or cyclosporine toxicity. In the last three groups diagnoses were biopsy-proved, and all samples were collected at the time of biopsy. TGF beta 1 was also measured in urine samples from 8, 11, 0, 9, 4, and 7 individuals, respectively, from each group. TGF beta 1 was not detected in plasma from any of the healthy controls or any of the MN patients, (detection limit of assay 0.1 ng/ml). By comparison, it was significantly increased in all groups of transplant recipients (unpaired t test, P < 0.01), but there were no significant differences between the transplant groups. Plasma TGF beta 1 level did not correlate with renal function (estimated by either serum creatinine or reciprocal creatinine), kidney donor age, recipient age, time since transplantation, or cyclosporine plasma trough level. TGF beta 1 was found in every urine sample tested from healthy controls, with a range from 1 ng/ml to 35 ng/ml. Among the 20 transplant patient urines tested, 2 were negative, 18 were positive but within the range determined for the healthy controls. There were no significant differences between the groups.
转化生长因子β（TGFβ1）是一种与多种疾病进程相关的促纤维化细胞因子。最近的报告表明TGFβ1在肾小球肾炎实验模型中发挥作用，这使得人们将注意力集中在TGFβ与人类疾病中肾纤维化形成的相关性上。本文报道的这项研究旨在调查肾移植受者体内是否能检测到循环中的活性TGFβ1，以及血浆水平是否与排斥反应发作相关，排斥反应是一个涉及炎症和纤维化的过程。我们利用市售抗体开发了一种用于检测活性TGFβ1的ELISA检测方法，并测量了43名健康对照者、11名患有膜性肾病（MN）且肾功能受损的患者、17名肾功能稳定的移植受者、27名急性细胞排斥患者、7名慢性血管排斥患者以及10名急性肾小管坏死和/或环孢素毒性患者的血浆水平。在最后三组中，诊断均经活检证实，所有样本均在活检时采集。每组分别还对8名、11名、0名、9名、4名和7名个体的尿液样本进行了TGFβ1检测。在任何健康对照者或任何MN患者的血浆中均未检测到TGFβ1（检测方法的检测限为0.1 ng/ml）。相比之下，所有移植受者组中的TGFβ1均显著升高（未配对t检验，P<0.01），但各移植组之间无显著差异。血浆TGFβ1水平与肾功能（通过血清肌酐或肌酐倒数估算）、肾脏供体年龄、受者年龄、移植后时间或环孢素血浆谷浓度均无相关性。在所有检测的健康对照者尿液样本中均发现了TGFβ1，范围为1 ng/ml至35 ng/ml。在检测的20份移植患者尿液中，2份为阴性，18份为阳性，但在健康对照者确定的范围内。各组之间无显著差异。
