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

采用免疫组化方法检测移植组织样本在移植收获和活体供肝移植后的不同情况下对窦内皮和胆道上皮的损伤、白细胞的粘附、粘附分子（ICAM-1）、HLA-DR和Kupffer细胞的活化情况。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。血管内皮损伤和白细胞粘附在移植物再灌注后一旦增加，可在数天内恢复。ICAM-1和HLA-DR的表达表现出相当延迟的增加，并与后来的急性排斥反应有关，这表明需要一种强效维持免疫抑制剂。与尸体肝移植相比，活体肝移植中由于供体疾病或长时间保存导致的移植前损伤被最小化。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的表达。此外，利用流式细胞术交叉匹配（FCXM）阳性血清，即抗HLA抗体阳性，通过组织交叉匹配研究抗体结合的位点和强度及其与HLA表达的关系。对于没有FCXM阳性的临床急性排斥反应，除HLA外，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。这些方法有望承担急性排斥反应的新分类，可作为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.