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

背景同种异体抗原的口服或门静脉给药下调了器官移植后的同种免疫应答和移植物存活。然而，供体特异性经门静脉输血（DST）的效果在啮齿动物模型中已有报道，在人类病例中未见报道。为探讨活体亲属肝移植（Living related donor liver transplantation，LRDLT）中经门静脉行DST能否提高临床和免疫学效果，对1999年3月至2001年12月间18例LRDLT患者进行了回顾性分析。7例患者给予Tac +类固醇方案（I. P. (-)组：n=7，平均年龄54± 9岁。). 11例患者除腹腔注射Tac +激素外，术后经中结肠静脉插入门静脉导管行DST。（+）组：n=11，平均年龄45± 15岁）。观察两组免疫抑制和排斥反应的减轻情况及免疫学指标 ...更多信息 结果IP（+）组1个月内甲泼尼龙和泼尼松龙总量小于IP（-）组，差异有统计学意义。IP（+）组1个月内的Tac量及Tac谷值均低于IP（-）组，差异有统计学意义。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、1个月后的急性细胞排斥反应（ACR）发生率或总ACR发生率均低于IP（-）组。在经门静脉的DST患者中证实了移植物中供体型CD 56 + T细胞的巨嵌合体。相反，非DST患者的移植肝中受体型CD 56 +T细胞增加。DST（+）组术后第1天IL-10水平高于DST（-）组。供体型NKT细胞尤其是CD 56 + T细胞可能通过否决机制和抗独特型网络机制诱导免疫耐受。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。少

项目成果

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。

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。

Oya H, Sato Y, et al.: "Changes in serum cytokine levels and donor-specific transfusion via portal vein during the early period following living related donor liver transplantation"Transplant Proc. 35(in press). (2003)

Oya H、Sato Y 等人：“活体相关供体肝移植后早期血清细胞因子水平的变化和通过门静脉的供体特异性输血”Transplant Proc。

Sato Y, et al: "Maerochimerism of donor type CD56+CD3+ T cells in donor specific transfusion via portal vein following living related donor liver transplantation"Hepato-Gastroenterology. 51 (in press). (2003)

Sato Y 等人：“活体相关供体肝移植后通过门静脉供体特异性输血中供体型 CD56 CD3 T 细胞的 Maerochimerism”肝胃肠病学。