Early immunosuppression withdrawal after living donor liver transplantation and donor stem cell infusion
Early immunosuppression withdrawal after living donor liver transplantation and donor stem cell infusion
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DOI：
10.1002/lt.20872
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发表时间：
2006-10-01
影响因子：
4.6
通讯作者：
Goldman, Michel
中科院分区：
文献类型：
--
作者：
Donckier, Vincent;Troisi, Roberto;Goldman, Michel
器官移植的长期效果仍然受到免疫抑制药物严重副作用的限制。因此，一个主要的问题是制定新的治疗方案，允许移植后免疫抑制治疗的撤回或减少。我们报告了3例前瞻性纳入原始协议的患者，该协议旨在促进活体肝移植中移植物的接受，采用高剂量抗胸腺细胞球蛋白移植后预处理，然后注射供体来源的干细胞。在2例患者中，早期免疫抑制剂撤药是可能的，没有随后的移植物恶化。在这2例病例中，体外研究显示，通过混合淋巴细胞培养物中对供体同种异体抗原的特异性低反应性评估免疫耐受指数。在第三例患者中，急性排斥反应在停止免疫抑制后迅速发生，在长期随访期间必须维持最低限度的免疫抑制。在这种情况下，与耐受患者相比，观察到明显不同的免疫反应性特征，因为在体外未观察到抗供体反应的特异性调节。值得注意的是，在随访期间，在3例患者中均未检测到巨嵌合体。总之，这些临床观察结果表明，尽管缺乏巨嵌合体，供体干细胞输注结合受体预处理可能允许肝移植后早期免疫抑制剂的撤销或最小化。
Long-term results of organ transplantation are still limited by serious side effects of immunosuppressive drugs. A major issue, therefore, is to elaborate novel therapeutic protocols allowing withdrawal or minimization of immunosuppressive therapy after transplantation. We report on 3 patients prospectively enrolled in an original protocol designed to promote graft acceptance in living donor liver transplantation, using posttransplant conditioning with high doses of antithymocyte globulin followed by injection of donor-derived stem cells. In 2 patients, early immunosuppression withdrawal was possible, without subsequent graft deterioration. In these 2 cases, in vitro studies showed indices of immunological tolerance as assessed by specific hyporesponsiveness to donor alloantigens in mixed lymphocytes culture. In the third patient, acute rejection rapidly occurred after discontinuation of immunosuppression, and minimal immunosuppression has to be maintained during long-term follow-up. In this case, a clearly distinct immunoreactive profile was observed as compared to tolerant patients, as no specific modulation of the antidonor response was observed in vitro. Of note, no macrochimerism could be detected in any of the 3 patients during the follow-up. In conclusion, these clinical observations demonstrated that, despite the absence of macrochimerism, donor stem cells infusion combined with recipient conditioning may allow early immunosuppression withdrawal or minimization after liver transplantation.