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

活体相关肝移植中通过门静脉注射供血完全停用免疫抑制剂

• 批准号: 12671147
• 负责人: SATO Yoshinobu
• 金额: $ 2.24万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671147/
• 关键词: living related liver transplantation; tance; ject; donor spic transfusion; intraportal administration of donor antigen; chimerism; NKT cell; immunosuppressant; Living-related liver transplantation; Chimerism; NKT cell; CD56^+T cell; DST; port

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

同种异体抗原的背景口服或门户给药可下调同种异体免疫反应，并在器官移植后延长移植物的存活。但是，在啮齿动物模型中已经报道了供体特异性输血（DST）通过门静脉的影响，在人类病例中尚未报道。我们调查了DST是否会在与生活相关的供体肝移植（LRDLT）中提高临床和免疫学益处。从1999年3月至2001年12月接受了LRDLT的18例患者。给出了7例TAC +类固醇方案（i.p。（ - ）组：n = 7，平均年龄为54±9y.o。）。除TAC +类固醇（i.p。（ +）组：n = 11，平均年龄45±15y.o。）外，还通过静脉介质插入的门户静脉导管进行了11例术后重复DST。在这两组中研究了有关免疫抑制和排斥反应以及免疫学分析的临床作用……在IP（+）组中，IP（+）组的甲基丙醇酮和泼尼松龙的总数均小于IP（ - ）组中的甲基甲基丙酮酮。 IP（+）组的TAC在一个月内的TAC数量和IP（ - ）组中的TAC水平统计较小。 IP（+）组中TAC的最低剂量显然小于IP（ - ）组中的TAC剂量，其统计显着性。急性细胞排斥（ACR）在一个月内和IP（+）组中ACR的总频率之后的频率往往小于IP（ - ）组中的ACR频率。通过门静脉，DST患者证实了移植物中供体型CD56+ T细胞的宏观chimerismism。相反的受体型CD56+T细胞在没有DST的患者的移植肝脏中增加。在LRDLT.Conclusions之后，DST（+）组的IL-10产生高于DST（ - ）组的IL-10组高于DST（ - ）组的IL-DST（ - ）组的产生。重复的DST通过门静脉静脉导致免疫抑制剂的快速降低。供体型NKT细胞，尤其是CD56+ T细胞，可能通过否决机制和抗IDiotype网络机制诱导耐受性。这些好处可能会在并发症和移植成本的频率上带来更多优势。较少的

项目成果

Sato Y, et al.: "Repeating intraportal donor specific transfusion may induce tolerance following adult living related donor liver transplantation"Hepato-Gastroenterology. 51. 601-606 (2003)

Sato Y 等人：“重复门静脉内供体特异性输血可能会在成人活体相关供体肝移植后诱导耐受性”肝胃肠病学。

Yoshinobu Sato: "Real-time measurement of anti-HBS level and donor-Specific transfusion via portal vein may reduce amount of HBIG after living rolated liver transplutable"The American Journal of Gastroenterology. 97(2). 488-489 (2002)

Yoshinobu Sato：“实时测量抗 HBS 水平和通过门静脉进行供体特异性输血可能会减少活体旋转肝移植后 HBIG 的量”《美国胃肠病学杂志》。

Yoshinobu Sato: "The new strategy of treatment for unresectable hepatocellular carcinoma in living related donor liver transplantation"Digestive Surgery. 17(S1). 94-94 (2000)

佐藤嘉信：“活体相关供体肝移植治疗不可切除肝细胞癌的新策略”消化外科。

Satoshi Yamamoto: "A successful positive crossmatch case treated with postoperative repeated donor whole bood administration via portal vein in adult living related partial liver transplantation"Transplantation Proceedings. 34(in press). (2002)

Satoshi Yamamoto：“在成人活体部分肝移植中通过门静脉重复给予供者全血术后成功的阳性交叉配型病例”移植论文集。

Yamamoto S, Sato Y, et al: "Morphologic examination of CD3-CD4bright cells in rat liver"Wound Rep Reg. 10. 241-244 (2002)

Yamamoto S、Sato Y 等人：“大鼠肝脏中 CD3-CD4bright 细胞的形态学检查”Wound Rep Reg。