Complete Withdraw from Immunosuppressants by Intraportal Administration of Donor Blood in Living-Related Liver Transplantation

背景：器官移植后，口服或门静脉注射同种异体抗原可下调同种异体免疫反应，延长移植物存活时间。然而，通过门静脉输注供者特异性输血(DST)的效果在啮齿动物模型中已有报道，在人类中尚未见报道。目的探讨门静脉DST在活体亲属供肝移植(LRDLT)中的临床和免疫学意义。7例患者接受Tac+类固醇方案(ip(-)组)，n=7，平均年龄54±9岁。)。除Tac+激素组(n=11，平均年龄45±15岁)外，其余11例均经结肠中静脉插入门静脉导管再次行DST。观察两组…在减少免疫抑制、减少排斥反应及免疫学分析方面的临床效果。结果IP(+)组1个月内甲泼尼龙和强的松龙总量均少于IP(-)组，差异有统计学意义。IP(+)组1个月内Tac量及谷值均显著低于IP(-)组。IP(+)组Tac最小剂量明显小于IP(-)组，差异有统计学意义。IP(+)组1个月内和1个月后急性细胞排斥反应(ACR)发生率或ACR总发生率均低于IP(-)组。DST患者通过门静脉证实供体CD56+T细胞在移植物中存在巨细胞嵌合体。相反，在无DST的患者移植肝中受体CD56+T细胞增加。在LRDLT后第1天，DST(+)组IL-10的产生高于DST(-)组。结论经门静脉重复DST导致免疫抑制药物的迅速减少。供体型NKT细胞，尤其是CD56+T细胞，可能通过否决机制和抗独特型网络机制诱导耐受。这些好处可能会在并发症发生率和移植成本方面带来更多优势。较少

Background Oral or portal administration of allogeneic antigens downregulates the alloimmune response and prolongs graft survival following organ transplantation. However, the effect of donor specific transfusion (DST) via portal vein has been reported in rodent models, there has not been reported in human cases. We investigated whether DST via portal vein would bring up the clinical and immunological benefits in living related donor liver transplantation (LRDLT).Methods The eighteen patients who underwent LRDLT from March 1999 to December 2001, were investigated. Seven patients were given the Tac + steroid regimen (I.P.(-) group : n=7, mean age 54±9y.o. ). Eleven patients were performed postoperative repeated DST via portal venous catheter inserted from vena colica media besides from the Tac + steroid (I.P.(+) group : n=11, mean age 45±15y.o.). The clinical effects about the reduction of immunosuppresions and the rejection, and the immunological analysis were studied in the two groups … More .Results Total amount of methylprednisolone and prednisolone within one month in IP(+) group was smaller than that in IP(-) group with statistical significance. Amount of Tac within one month and Trough level of Tac was statistically smaller in IP(+) group than that in IP(-) group. Minimum dose of Tac in IP(+) group was clearly smaller than that in IP(-) group with statistical significance. The frequency of acute cellular rejection (ACR) within one month and after one month or total frequency of ACR in IP(+) group tended to be less than those in IP(-) group. Macrochimerism of donor type CD56+ T cells in a graft were confirmed in patients with DST via the portal vein. Conversely recipient type CD56+T cells increased in the graft liver in patients without DST. IL-10 production of DST(+) group were higher than that of DST (-) group on day 1 after LRDLT.Conclusions The repeated DST via portal vein has brought the rapid reduction of immunosuppressants. Donor type NKT cells especially CD56+ T cells, may induce tolerance by veto mechanism and anti-idiotype network mechanism. These benefits might introduce more advantages in frequencies of complications and cost of transplantation. Less