Ricerc@Sapienza

Cytomegalovirus (CMV) continues to have a tremendous impact in transplant patients despite remarkable advances in its diagnosis, prevention and treatment. It can affect allograft function and increase patient morbidity and mortality through a number of direct and indirect effects. Patients may develop asymptomatic viremia, CMV syndrome or tissue-invasive disease. Emerging data suggests that immunologic monitoring may be useful in predicting the risk of late onset CMV disease. However, this herpesvirus is one of the most complex viruses to infect humans, and the intricacy of both innate and adaptive immune responses means that it has not yet been fully characterized. In this scenario while interferons (IFN) are universally acknowledged for their antiviral and immunostimulatory functions, there is increasing appreciation of the detrimental effects of inappropriate, excessive, or mistimed type I IFN responses in viral infections. Hence, this project will allow to determine the combined effect of organ or stem cell transplantation and immunosuppressive drugs on type I and III IFN response and whether IFN related immune function profiling/monitoring can be used to predict CMV infections and rejections. In particular, we plan to assess the incidence, timing and impact of CMV viremia in patients receiving solid organ or hematopoietic stem cell transplantation and to determine the level of viremia associated with adverse clinical outcomes. Moreover, the evaluation of IFN signature, of genetic variants in selected IFN-I/III pathways and the ability of PBMC, T cells and macrophages to up-regulate IFN-stimulated gene response after in vitro exposure to IFN will be performed before and after transplantation. A prediction model integrating virological, immunological, therapeutic and clinical data will be development and will be used to bring personalized medicine into clinical practice in the transplant population.