Persistent cytomegalovirus infection is associated with increased expression of TGF-beta1, PDGF-AA and ICAM-1 and arterial intimal thickening in kidney allografts.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Persistent CMV infection in kidney allografts was associated with increased vascular changes and increased expression of TGF-beta1, PDGF-AA and ICAM-1.
Helanterä
Ilkka
I
Department of Virology, Helsinki University Hospital and Univeristy of Helsinki, Finland.
Loginov
Raisa
R
Koskinen
Petri
P
Törnroth
Tom
T
Grönhagen-Riska
Carola
C
Lautenschlager
Irmeli
I
D000328:Adult; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; D018799:Intercellular Adhesion Molecule-1