Donckier Vincent, Troisi Roberto, Le Moine Alain, Toungouz Michel, Ricciardi Salvatore, Colle Isabelle, Van Vlierberghe Hans, Craciun Ligia, Libin Myriam, Praet Marleen, Noens Lucien, Stordeur Patrick, Andrien Marc, Lambermont Micheline, Gelin Michel, Bourgeois Nadine, Adler Michael, de Hemptinne Bernard, Goldman Michel
Medicosurgical Department of Hepatogastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Brussels.
Liver Transpl. 2006 Oct;12(10):1523-8. doi: 10.1002/lt.20872.
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.
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，一个主要问题是制定新的治疗方案，以便在移植后停用免疫抑制治疗或使其最小化。我们报告了3例前瞻性纳入一项原始方案的患者，该方案旨在促进活体供肝移植中的移植物接受，采用高剂量抗胸腺细胞球蛋白进行移植后预处理，随后注射供体来源的干细胞。在2例患者中，早期停用免疫抑制是可行的，且随后移植物没有恶化。在这2例病例中，体外研究显示了免疫耐受指标，这是通过混合淋巴细胞培养中对供体同种异体抗原的特异性低反应性来评估的。在第3例患者中，停用免疫抑制后迅速发生急性排斥反应，在长期随访期间必须维持最小剂量的免疫抑制。在该病例中，与耐受患者相比，观察到明显不同的免疫反应特征，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，3例患者中均未检测到巨嵌合体。总之，这些临床观察表明，尽管没有巨嵌合体，但供体干细胞输注联合受体预处理可能允许肝移植后早期停用免疫抑制或使其最小化。
