Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
The Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Am J Transplant. 2021 Feb;21(2):876-882. doi: 10.1111/ajt.16224. Epub 2020 Aug 30.
By presenting the first case report of true operational tolerance in an intestinal transplant patient, we aim to demonstrate that tolerance is possible in a field that has been hampered by suboptimal outcomes. Although operational tolerance has been achieved in liver and kidney transplantation, and some intestinal transplant patients have been able to decrease immunosuppression, this is the first instance of true operational tolerance after complete cessation of immunosuppression. A patient received a deceased-donor small intestinal and colon allograft with standard immunosuppressive treatment, achieving excellent graft function after overcoming a graft-versus-host-disease episode 5 months posttransplant. Four years later, against medical advice, the patient discontinued all immunosuppression. During follow-up visits 2 and 3 years after cessation of immunosuppression, the patient exhibited normal graft function with full enteral autonomy and without histological or endoscopic signs of rejection. Mechanistic analysis demonstrated immune competence against third party antigen, with in vitro evidence of donor-specific hyporesponsiveness in the absence of donor macrochimerism. This proof of principle case can stimulate future mechanistic studies on diagnostic and therapeutic strategies, for example, cellular therapy trials, that can lead to minimization or elimination of immunosuppression and, it is hoped, help revitalize the field of intestinal transplantation.
通过报告首例肠道移植患者真正的操作性耐受病例，我们旨在证明在一个因结果不理想而受到阻碍的领域中，耐受是可能的。尽管在肝和肾移植中已经实现了操作性耐受，并且一些肠道移植患者已经能够减少免疫抑制，但这是在完全停止免疫抑制后首次出现真正的操作性耐受。一名患者接受了一名已故供体的小肠和结肠同种异体移植，并接受了标准免疫抑制治疗，在克服移植后移植物抗宿主病发作 5 个月后，实现了优异的移植物功能。四年后，尽管有医疗建议，患者还是停止了所有免疫抑制。在停止免疫抑制后的 2 年和 3 年随访期间，患者表现出正常的移植物功能，具有完全肠内自主性，并且没有排斥反应的组织学或内镜迹象。机制分析显示对第三方抗原具有免疫能力，在不存在供体嵌合体的情况下具有供体特异性低反应性的体外证据。这一原理验证病例可以激发未来关于诊断和治疗策略的机制研究，例如细胞治疗试验，这可能导致免疫抑制的最小化或消除，并有望重振肠道移植领域。
