DNA MICROARRAY-BASED GENE EXPRESSION PROFILES OF CYTOMEGALOVIRUS INFECTION AND ACUTE REJECTION IN LIVER TRANSPLANTS

Abstract An association between cytomegalovirus (CMV) infection and alloresponse has been suggested. CMV increases inflammation and adhesion molecule expression in graft, and induces cytokines and growth factors, linked with transplant vasculopathy and chronic rejection. We have investigated the gene expression of various inflammatory factors in the CMV-associated immune response and compared this with the immune response of acute rejection in liver transplants by using DNA microarray technology. Gene expression was studied at mRNA level in biopsies from liver transplant patients experiencing CMV infection or acute rejection. RNA extracted from liver grafts after reperfusion was used as control material. Among the strongly upregulated genes in the specimens obtained from liver transplants during CMV infection were IFN-γ, caspases 1 and 3, granzymes A and B, TGF-β receptors II and III, IL-10 receptor α, VCAM-1, TNF receptor, IL-4, TNF-α, IL-10, IL-2 receptor β, IL-1β, PDGF-receptor β, vascular adhesion protein-1, TGF-β2, and ICAM-1. In biopsies with acute liver allograft rejection, the most significantly upregulated genes were MHC class II, IFN-γ, caspases 1 and 3, IL-2R β and γ, granzymes A and B, VLA-4, L-selectin, E-selectin, VCAM-1, and IL-1β. Upregulated genes common for CMV and alloresponse were granzyme A and B, E-selection, IFN-γ, VCAM-1, VLA-4, TNF, caspases 1, 3, and 8, and PDGF. Microarray analysis defined different entities in the immune responses of CMV infection and acute rejection. The differences and similarities of the gene expression profiles related to those in CMV infection and rejection may help to understand the intragraft immunologic events.