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4 例手移植患者中使用贝利尤单抗的获益和局限性。

Benefits and limitations of belatacept in 4 hand-transplanted patients.

机构信息

Department for Visceral, Thoracic and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria.

Oxford University Hospitals NHS Foundation Trust, Oxford Transplant Centre, Oxford, UK.

出版信息

Am J Transplant. 2017 Dec;17(12):3228-3235. doi: 10.1111/ajt.14440. Epub 2017 Sep 13.

Abstract

Belatacept (cytotoxic T-lymphocyte-associated protein 4 Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor-specific antibodies (DSAs) make it an interesting agent in hand transplantation. To reduce calcineurin inhibitor immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand-transplanted patients at month 4 and at 6, 9, and 13 years after hand-forearm transplantation. Patients received 5 mg/kg belatacept every 2 weeks, and the dosing interval was extended to 4 weeks after 5 applications. Belatacept was initially well tolerated in all cases. Two patients were weaned to a low-dose tacrolimus monotherapy together with monthly belatacept applications. One patient is taking belatacept with lowered tacrolimus and sirolimus trough levels. A fourth patient had significant levels of DSAs at time of conversion and progressed to a severe necrotizing rejection early despite an unaltered baseline immunosuppression. Finger skin necrosis and histologic signs of severe chronic allograft vasculopathy eventually led to amputation of the graft. Implementation of belatacept can be beneficial in hand transplantation. However, our findings indicated both potential and caution and reflection of the immunologic state at the time of conversion.

摘要

贝利尤单抗(细胞毒性 T 淋巴细胞相关蛋白 4 Ig)是一种新兴的肾移植治疗方法。由于其无肾毒性且可能对供体特异性抗体(DSA)的产生具有抑制作用,因此在手部移植中具有一定的应用前景。为了减少钙调磷酸酶抑制剂的免疫抑制作用并保留肾功能,我们在 4 名手部移植患者的术后第 4 个月、第 6、9 和 13 年,在治疗方案中添加了贝利尤单抗。患者每 2 周接受 5mg/kg 的贝利尤单抗治疗,5 次应用后,将给药间隔延长至 4 周。所有患者均耐受良好。2 名患者停用了低剂量他克莫司单药治疗,改为每月应用贝利尤单抗。1 名患者接受贝利尤单抗治疗,同时降低了他克莫司和西罗莫司谷浓度。第 4 名患者在转换时就已经有明显的 DSA 水平,尽管免疫抑制基线未改变,但仍在早期进展为严重的坏死性排斥反应。手指皮肤坏死和严重慢性移植物血管病的组织学迹象最终导致移植物截肢。在手部移植中应用贝利尤单抗可能是有益的。然而,我们的发现表明,在转换时需要考虑免疫状态的潜在风险和谨慎性。

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