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

移植物组织样本，采取在移植收获和活体肝移植后的各种场合，通过免疫组化检查肝窦内皮细胞和胆管上皮细胞，白细胞粘附，粘附分子（ICAM-1），HLA-DR，和枯否细胞的活化损伤。分析这些组织学参数与急性排斥反应、免疫抑制和其他并发症的关系。窦状隙内皮损伤和白细胞粘附，在移植物再灌注后一旦增加，在几天内恢复。ICAM-1和HLA-DR表达呈延迟性增高，并与术后急性排斥反应有关，提示需要强免疫抑制剂维持。与尸体肝移植相比，活体肝移植中由于供体疾病或长期移植物保存而导致的移植前移植物损伤最小化。然而，再灌注后的急性期反应触发内皮细胞、中性粒细胞和血小板的活化，并进一步导致细胞因子释放或粘附分子和HLA. Further，使用流式细胞术交叉配型（FCXM）阳性的血清，即抗HLA抗体阳性的血清，通过组织交叉配型研究抗体结合的位点和强度及其与HLA表达的关系。对于FCXM阴性的临床急性排斥反应，HLA以外的其他可能导致抗体介导的排斥反应的抗原也正在通过组织化学方法进行研究，这些方法有望对急性排斥反应进行新的分类，这可能是未来鉴别治疗或排斥反应的有用工具。

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.