Helanterä Ilkka, Loginov Raisa, Koskinen Petri, Törnroth Tom, Grönhagen-Riska Carola, Lautenschlager Irmeli
Department of Virology, Helsinki University Hospital and Univeristy of Helsinki, Finland.
Nephrol Dial Transplant. 2005 Apr;20(4):790-6. doi: 10.1093/ndt/gfh714. Epub 2005 Feb 16.
Cytomegalovirus (CMV) is a suggested risk factor for the development of chronic allograft nephropathy. Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) are important molecules in this process. We analysed the impact of persistent CMV infection in kidney allografts on the expression of growth factors, adhesion molecules and inflammation markers.
In a population of 172 renal transplant recipients, CMV was diagnosed in 82 patients by pp65 antigenaemia test and viral cultures. Biopsies taken after CMV infection were available from 48 of the 82 patients for the demonstration of CMV antigens by immunohistochemistry and in situ DNA hybridization. Biopsy material for further analyses was available from 16 CMV patients. Five patients with no previous CMV infection were used as controls. Biopsy histology was scored according to Banff 97 classification.
In 11 out of 16 patients, persistent CMV antigens and/or DNA were demonstrated in the biopsy >2 months after the last positive finding in blood or urine. Increased expression of TGF-beta1 was recorded in tubuli and in arterial endothelium in biopsies with a positive CMV finding compared with controls. Also, the expression of PDGF-AA was increased in tubuli and somewhat in arterial endothelium in CMV-positive biopsies. The expression of intercellular adhesion molecule-1 (ICAM-1) was increased significantly in peritubular capillary endothelium. Vascular intimal thickening was increased in the biopsies with persistent CMV infection.
Persistent CMV infection in kidney allografts was associated with increased vascular changes and increased expression of TGF-beta1, PDGF-AA and ICAM-1.
巨细胞病毒（CMV）被认为是慢性移植肾肾病发生的一个风险因素。转化生长因子-β（TGF-β）和血小板衍生生长因子（PDGF）是这一过程中的重要分子。我们分析了肾移植受者中持续性CMV感染对生长因子、黏附分子和炎症标志物表达的影响。
在172例肾移植受者中，通过pp65抗原血症检测和病毒培养在82例患者中诊断出CMV感染。82例患者中有48例在CMV感染后进行了活检，通过免疫组织化学和原位DNA杂交来显示CMV抗原。16例CMV感染患者有用于进一步分析的活检材料。5例既往无CMV感染的患者作为对照。活检组织学根据Banff 97分类进行评分。
16例患者中有11例在血液或尿液中最后一次阳性发现后2个月以上的活检中显示有持续性CMV抗原和/或DNA。与对照组相比，CMV检测呈阳性的活检中，肾小管和动脉内皮中TGF-β1的表达增加。此外，CMV阳性活检中肾小管和动脉内皮中PDGF-AA的表达也有所增加。肾小管周围毛细血管内皮中细胞间黏附分子-1（ICAM-1）的表达显著增加。持续性CMV感染的活检中血管内膜增厚增加。
肾移植受者中持续性CMV感染与血管变化增加以及TGF-β1、PDGF-AA和ICAM-1的表达增加有关。
