Research for Immunosuppressive Therapy Adjusted to Interindvidual and Chronological Variations of Graft Antigenicity in Living Donor Liver Transplantation.

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Graft tissue samples, taken at graft harvesting and at various occasions after living donor liver transplantation, were examined by immunohistochemistry for injuries in sinusoidal endothelium and biliary epithelium, adhesion of leukocytes, adhesion molecule (ICAM-1), HLA-DR,and activation of Kupffer cells. These histological parameters were analyzed in relationship with acute rejection, immunosuppression, and other complications.Sinusoidal endothelial injury and leukocyte adhesion, once increased after graft reperfusion, recovered within several days. Expression of ICAM-1 and HLA-DR showed a rather delayd increase and was associated with later acute rejection, suggesting the need for a strong maintenance immunosuppressant. In contrast to cadaveric liver transplantation, pretransplant graft injuries due to donor illness or long graft preservation are minimized in living donor transplantation. Acute phase responses after reperfusion, however, trigger activations of endothelial cells, neutrophil leukocytes, and platelets, and further lead to cytokine release or expressions of adhesion molecules and HLA.Furthermore, using sera positive for flow cytometry crossmatch (FCXM), i.e.positive for anti-HLA antibodies, sites and intensity of antibody binding and their relationship with HLA expressions are being investigated by tissue crossmatch. For clinical acute rejection without positive FCXM,other antigens than HLA that potentially lead to antibody-mediated rejection are also being investigated by histochemical methods.These approaches are expected to bear a new classification of acute rejection that can be a useful tool of future differential treatment or rejection.