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.

捐献者在手术后2周出院，没有任何手术并发症。术后病程也很顺利。采用胸腺球蛋白、FK506和霉酚酸酯联合门静脉内输注供体特异性抗原^[2]的无类固醇方案进行免疫抑制。无出血和胰漏。移植后15天她出院了。免疫学分析显示移植后第7天Th2型细胞因子白细胞介素10活化（图1）。移植后8个月混合淋巴细胞反应显示供者特异性免疫抑制。她的低血糖症状缓解。术后6个月体重下降56 kg，HbA1c降至5.1%。日本首例同时采用生理性肠道引流和无激素方案的LRPT获得成功。尸体胰腺移植术后肠内引流明显增加。在活体部分胰腺移植中，在谨慎的外科技术下，肠道引流被认为是生理性重建的一种选择。LRPT对I型糖尿病的治疗可能是预防尸体胰腺移植并发症的有效方法。我们已经报道了活体肝移植中供体特异性输血的门静脉内给药。在这项研究中，证明了供体白细胞的门静脉内给药也可能是有效的诱导治疗LRPT的无类固醇方案，如我们的经验，活体肝移植。

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