Hecker Jens M, Lorenz Ralf, Appiah Richard, Vangerow Burkhard, Loss Martin, Kunz Robert, Schmidtko Jan, Mengel Michael, Klempnauer Jürgen, Piepenbrock Siegfried, Dickneite Gerhard, Neidhardt Helge, Rückoldt Horst, Winkler Michael
Klinik für Viszeral- und Transplantationschirurgie, Zentrum Anästhesiologie, Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
Transplantation. 2002 Mar 15;73(5):688-94. doi: 10.1097/00007890-200203150-00006.
Early rejection of discordant porcine xenografts in primate recipients is initiated by the intragraft binding of either preformed (hyperacute xenograft rejection) or induced (acute vascular rejection) antiporcine recipient antibodies with subsequent complement activation via the classical pathway. We have investigated the efficacy of the supplemental administration of C1-inhibitor (C1-INH), a specific inhibitor of the classical complement activation pathway, for prophylaxis of xenograft rejection in a pig to primate kidney xenotransplantation setting.
Based on the results of pharmacokinetic studies performed in two nontransplanted monkeys, supplemental C1-INH therapy was administered daily to three Cynomolgus monkeys receiving a life-supporting porcine kidney transplant together with cyclophosphamide-induction/cyclosporine A/mycophenolat-mofetil/steroid immunosuppressive therapy.
In the three monkeys receiving porcine kidney xenografts and continuous C1-INH treatment none of the grafts underwent hyperacute rejection; all xenografts showed initial function. Recipient survival was 13, 15, and 5 days. No graft was lost due to acute vascular rejection. All animals died with a functioning graft (latest creatinine 96, 112, and 96 micromol/liter) due to bacterial septicemia.
We conclude that, in our model, supplemental C1-INH therapy together with a standard immunosuppressive regimen can be helpful for prevention of xenograft rejection in a pig to primate kidney xenotransplantation setting. The optimal dose and duration of C1-INH treatment, however, has yet to be determined.
灵长类动物受体对不协调性猪异种移植物的早期排斥反应，是由预先形成的（超急性异种移植物排斥反应）或诱导产生的（急性血管排斥反应）抗猪受体抗体在移植物内结合，随后通过经典途径激活补体所引发的。我们研究了补充给予C1抑制剂（C1-INH）（经典补体激活途径的特异性抑制剂）在猪到灵长类动物肾异种移植模型中预防异种移植物排斥反应的效果。
基于在两只未进行移植的猴子身上进行的药代动力学研究结果，对三只接受维持生命的猪肾移植的食蟹猴，在给予环磷酰胺诱导/环孢素A/霉酚酸酯/类固醇免疫抑制治疗的同时，每日补充C1-INH治疗。
在三只接受猪肾异种移植并持续接受C1-INH治疗的猴子中，没有移植物发生超急性排斥反应；所有异种移植物均显示出初始功能。受体存活时间分别为13天、15天和5天。没有移植物因急性血管排斥反应而丢失。所有动物均因细菌性败血症在移植物仍有功能时死亡（最后肌酐水平分别为96、112和96微摩尔/升）。
我们得出结论，在我们的模型中，补充C1-INH治疗联合标准免疫抑制方案有助于预防猪到灵长类动物肾异种移植中的异种移植物排斥反应。然而，C1-INH治疗的最佳剂量和持续时间尚未确定。
