巨细胞病毒感染期间肾移植受者尿中转化生长因子-β(1)排泄增加。

Increased urinary excretion of transforming growth factor-beta(1) in renal transplant recipients during cytomegalovirus infection.

作者信息

Helanterä Ilkka, Teppo Anna-Maija, Koskinen Petri, Törnroth Tom, Grönhagen-Riska Carola, Lautenschlager Irmeli

机构信息

Department of Virology, Helsinki University Central Hospital and University of Helsinki, Meilahti, FIN-00029 HUS, Helsinki, Finland.

出版信息

Transpl Immunol. 2006 Jan;15(3):217-21. doi: 10.1016/j.trim.2005.11.001. Epub 2005 Dec 22.

DOI:10.1016/j.trim.2005.11.001

PMID:16431289

Abstract

AIMS

Cytomegalovirus (CMV) is a suggested risk factor for chronic allograft nephropathy, and transforming growth factor-beta (TGF-beta) is a key fibrogenic molecule in this process. CMV has been shown to induce the expression of TGF-beta and several cytokines. We analyzed the impact of CMV on urinary excretion of TGF-beta, ICAM-1, TNF-alpha and correlated findings with biopsy histology.

MATERIAL

Urine samples from 46 renal transplant recipients were available for the study. Urine samples were taken when CMV infection was suspected, or for controlling of proteinuria or bacteriuria.

METHOD

CMV was diagnosed by antigenemia and viral cultures. Patients with previous CMV infection were excluded from the analysis. Urine samples were analyzed by ELISA-method to detect the levels of TNF-alpha, ICAM-1 and TGF-beta(1). Banff '97 criteria were used for scoring of protocol biopsies taken 6 months after transplantation.

RESULTS

At the time of the urine collection, 13/46 patients had CMV infection. Eight patients with no CMV infection were used as controls. TGF-beta(1) was significantly increased in the CMV group (samples taken mean 137+/-79 days post-transplantation) compared to controls (samples 139+/-64 days post-transplantation) (51.1+/-28.0 vs. 13.3+/-6.7 ng/mmol crea, p<0.001). No differences in the levels of other molecules were recorded. In the biopsies, interstitial fibrosis was significantly increased in the CMV group compared to controls.

CONCLUSIONS

Urinary excretion of TGF-beta(1) was increased in patients during CMV infection. This was associated with increased fibrosis in the biopsies.

摘要

目的

巨细胞病毒（CMV）被认为是慢性移植肾肾病的一个风险因素，而转化生长因子-β（TGF-β）是这一过程中的关键促纤维化分子。已有研究表明，CMV可诱导TGF-β及多种细胞因子的表达。我们分析了CMV对TGF-β、细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）尿排泄量的影响，并将相关结果与活检组织学进行了关联分析。

材料

本研究获取了46例肾移植受者的尿液样本。当怀疑有CMV感染时采集尿液样本，或为控制蛋白尿或菌尿而采集。

方法

通过抗原血症和病毒培养诊断CMV。既往有CMV感染的患者被排除在分析之外。采用酶联免疫吸附测定（ELISA）法分析尿液样本，以检测TNF-α、ICAM-1和TGF-β（1）的水平。使用Banff '97标准对移植后6个月进行的方案活检进行评分。

结果

在采集尿液时，46例患者中有13例发生CMV感染。8例无CMV感染的患者作为对照。与对照组（移植后139±64天采集样本）相比，CMV组（移植后平均137±79天采集样本）的TGF-β（1）显著升高（51.1±28.0对13.3±6.7 ng/mmol肌酐，p<0.001）。其他分子水平未发现差异。在活检中，与对照组相比，CMV组的间质纤维化显著增加。