Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

Abstract

Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular damage during HCMV infection, we investigated the levels of soluble markers during HCMV infection in relationship to EC levels and also preceding the acute rejection episodes. Of 46 kidney transplant patients, plasma levels of von Willebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-sel) were analyzed during the course of HCMV infection. Plasma levels of VWF and sVCAM-1 increased twofold during severe HCMV infection. Moreover, the plasma levels of VWF correlated with detectable cytomegalic and noninfected ECs in blood. The kinetics of changes in VWF and ECs (CEC and EC) demonstrated the relationship with HCMV-induced vascular damage. Levels of sICAM-1 and sE-sel in plasma did not significantly change during HCMV infection. Interestingly, the combination of HCMV infection and preceding acute transplant rejection caused the highest increases of VWF and sVCAM-1 plasma levels, reflecting an enhanced susceptibility for endothelial damage at the moment of infection. CMV infection is associated with vascular damage, and the vascular damage during CMV infection is enhanced if patients experienced acute rejection before CMV infection.