Immunosuppression for pancreatic islet transplantation
Immunosuppression for pancreatic islet transplantation
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DOI：
10.1016/j.transproceed.2003.12.035
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发表时间：
2004-03-01
影响因子：
0.9
通讯作者：
Morel, P
中科院分区：
文献类型：
--
作者：
Berney, T;Buhler, LH;Morel, P
胰岛移植方案必须考虑免疫抑制剂的致糖尿病性/胰岛毒性，免疫抑制剂即皮质类固醇和钙调磷酸酶抑制剂，最显著的是他克莫司。埃德蒙顿研究小组开发的以西罗莫司为基础、不含类固醇、低剂量他克莫司的治疗方案是一项重大突破，使胰岛移植后1年的胰岛素依赖率从13%提高到80%。缺点包括西罗莫司的副作用和3年时胰岛素依赖性降低至50%，后者归因于他克莫司暴露时间延长。目前探索的他克莫司的替代品包括环孢霉素、吗替麦考酚酯和新型药物FTY 720。近期的前景包括通过使用淋巴细胞耗竭抗体（抗胸腺细胞球蛋白、campath-1H、hOKT 3 gamma 1 [ala，ala]）或共刺激阻断（抗CD 154 mAb、CTLA 4-IG）策略实现“适当耐受”。
Protocols for islet transplantation have to take into account the diabetogenicity/islet toxicity of the immunosuppressive agents, namely corticosteroids and calcineurin inhibitors, most notably tacrolimus. The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen was a significant breakthrough that allowed the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year. Drawbacks include the side effects of sirolimus and the reduction in insulin independence to 50% at 3 years, the latter being attributed to prolonged tacrolimus exposure. Currently explored alternatives to tacrolimus include cyclosporine, mycophenolate mofetil, and the novel agent FTY 720. Perspectives for the near future involve the achievement of "prope tolerance" by strategies using lymphocyte-depleting antibodies (anti-thymocyte globulin, campath-1H, hOKT3gamma1 [ala,ala]), or costimulatory blockade (anti-CD154 mAbs, CTLA4-Ig).