Development of new immunosuppression by intra-portal administration of donor specific miss-match antigen in pancreas transplantation

在胰腺移植中通过门静脉内施用供者特异性错配抗原开发新的免疫抑制

• 批准号: 17390346
• 负责人: SATO Yoshinobu
• 金额: $ 10.96万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390346/
• 关键词: Living related pancreas transplantation; type I diabetes mellitus; intra-portal donor specific transfusion; Torelance; Rejection; Steroid free regimen; donor pancreas transplantation; 生体膵移植; I型糖尿病; キメリズム; ドナー抗原門脈内投与; 同所性部分膵臓移植

Donor discharged 2 weeks after surgery without any surgical complication. Recipient's postoperative course was also uneventful. Immunosuppresion was performed by steroid free regimen using thymoglobulin and FK506 and MMF with intraportal infusion of donor specific antigens^2. There were neither hemorrhage nor pancreatic leakage. She discharged 15 days after transplantation. Immunological analysis revealed of activation of interleukin 10 of Th2 type cytokine on day 7 after transplantation(Fig1). Mixed lymphocyte reaction demonstrated the donor specific immunosuppression at 8 month after transplantation. She released from hypoglycemia. Her body weight decreased by 56kg and HbA1c decreased to 5.1% for 6 months after the operation. There are no any rejection until now.The first case of both physiologic enteric drainage and steroid free regiment were successfully performed in LRPT in Japan. Enteric drainage has remarkably increased in cadaver pancreas transplantation. In living partial pancreas transplantation, the enteric drainage is considered to be one option as physiologic reconstruction under careful surgical technique. LRPT might be very useful therapy for type I diabetes mellitus for preventing diabetic complication with cadaver pancreas transplantation. We have already reported about the intraportal administration of donor specific transfusion in living related liver transplantation. In this study, it was demonstrated that the intraportal administration of donor leukocytes might be also effective as induction therapy for steroid free regiment in LRPT such as our experienced of living related liver transplantation.

手术后2周出院，没有任何手术并发症。接受者的术后课程也很顺利。使用胸腺球蛋白和FK506和MMF通过供体特异性抗原^2的胸腺球蛋白和FK506和MMF通过类固醇方案进行免疫供应。既没有出血也没有胰腺泄漏。她在移植后15天出院。免疫学分析揭示了移植后第7天的Th2型细胞因子的白介素10的激活（图1）。混合淋巴细胞反应表明，移植后8个月，供体特异性免疫抑制。她从低血糖释放。手术后6个月，她的体重下降了56公斤，HBA1C降至5.1％。到目前为止，还没有任何拒绝。在日本LRPT成功地进行了生理肠排水和无类固醇团的第一个案例。在尸体胰腺移植中，肠排水已大大增加。在生存的部分胰腺移植中，在仔细的手术技术下，肠管排水被认为是生理重建的一种选择。对于I型糖尿病，LRPT可能是非常有用的治疗方法，可预防尸体胰腺移植糖尿病并发症。我们已经报道了在生活相关肝移植中捐赠者特异性输血的体内给药。在这项研究中，证明供体白细胞的体内给药也可能是有效的，作为LRPT中无类固醇团的诱导疗法，例如我们对生活相关的肝移植经验丰富。

项目成果

Present status of pancreas transplantation in Japan-donation predominantly from marginal donors and modified surgical technique: Report of Japan pancreas transplantation registry

• DOI: 10.1016/j.transproceed.2008.01.047
• 发表时间: 2008-03-01
• 期刊: TRANSPLANTATION PROCEEDINGS
• 影响因子: 0.9
• 作者: Ishibashi, M.;Ito, T.;Kanazawa, Y.
• 通讯作者: Kanazawa, Y.

First experience of living-donor partial pancreas transplantation by new immunosuppression protocol with intra-portal donor specific antigen transfusion

采用门静脉内供体特异性抗原输注新免疫抑制方案进行活体部分胰腺移植的首次经验

• 发表时间: 2007
• 作者: Ishibashi;M;Ishibashi;M;Ito;T;Sugitani;A;Furukawa;H;Sekiguchi;S;Gotoh;M;Teraoka;S;Sato;Y,;et. al.;Yoshinobu Sato
• 通讯作者: Yoshinobu Sato