In recent years, transplantation research has focused mainly on solving the problem of acute rejection in transplant recipients. These research efforts have been very successful in that acute rejection has become treatable under normal circumstances and has led to excellent short-to-mid term allograft survival. However, we still need to face reality in that the available treatment options are not effective in preventing the onset of chronic rejection and fibrosis, which are key to the relatively poor long-term survival for transplant patients. For this reason, we examined immunological phenomena in experimental and translational terms which may affect the long-term graft survival.
In January 2013 we published in the American Journal of Transplantation a work entitled “Inhibition of Innate Co-Receptor TREM-1 Signaling Reduces CD4+ T Cell Activation and Prolongs Cardiac Allograft Survival”. In this work we studied a receptor of the innate immune system (TREM-1) on antigen-presenting cells and demonstrated its influence on the initiation of chronic rejection with consecutive allograft fibrosis. Inhibition of this receptor of the innate immune system reduced chronic rejection significantly, prolonged graft survival and prevented the formation of graft fibrosis. Interestingly enough, temporary inhibition of this receptor, in order to prevent an initial immune activation, achieved long-term graft survival.
In June 2013 we published in the Journal of Hepatology a work entitled "Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation". The basis for this translational work is that biliary complications are a major cause of morbidity, mortality and graft failure after liver transplantation. In this published work donor bile ducts were studied longitudinally in terms of their epithelial integrity in the course of explantation towards transplantation. Evaluating bile duct architecture and integrity with a newly developed bile-duct-damage-score we detected a significant epithelial damage in the bile duct already during cold preparation, before transplantation, which further increased after reperfusion injury. With this regard, normal tight junction architecture and thus barrier function of the bile duct epithelium at times before transplantation was already highly disturbed. These lesions were found to correlate with the clinical outcome of these patients. Thus, one can conclude from this study that even before liver transplantation a relevant damage to the bile duct is detectable in patient, and this damage is a negative prognostic marker for the development of biliary complications and graft failure after liver transplantation.
Based on these already published results will now continue working in an experimental, translational and clinical approach to achieve better understanding of the immunologic phenomenon of chronic rejection and biliary complications after liver transplantation. For this goal immunological and molecular signaling cascades are investigated in order to establish new treatment options for chronic allograft damage.