Department of Surgery, Columbia University Irving Medical Center.
Columbia University College of Dental Medicine.
Curr Opin Organ Transplant. 2022 Apr 1;27(2):119-125. doi: 10.1097/MOT.0000000000000958.
The intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to low volume of transplants and few centers with experience, there is paucity of evidence-based, standardized, and effective therapeutic regimens. We herein review the most recent data about immunosuppression, focusing on novel and emerging therapies.
Recent data are moving the field toward increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mammalian target of rapamycin inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for tumor necrosis factor-α inhibition, α4β7 integrin inhibition, microbiome modulation, desensitization protocols, and tolerance induction strategies. We also highlight emerging novel therapies for GVHD, especially the promising role of Janus kinase inhibition.
New insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.
肠道是免疫最复杂的实体器官同种异体移植,排斥反应和移植物抗宿主病(GVHD)的风险最大。需要高水平的免疫抑制,进一步增加发病率。由于移植数量少,经验丰富的中心也少,因此缺乏基于证据的标准化和有效的治疗方案。本文综述了关于免疫抑制的最新数据,重点介绍了新出现的治疗方法。
最近的数据使该领域越来越倾向于增加使用巴利昔单抗,并考虑使用阿仑单抗进行诱导,同时包括雷帕霉素抑制剂和代谢抑制剂进行维持。对于排斥反应,我们强调了肿瘤坏死因子-α抑制、α4β7 整合素抑制、微生物组调节、脱敏方案和诱导耐受策略的新作用。我们还强调了用于 GVHD 的新兴新型疗法,特别是 Janus 激酶抑制的有前途的作用。
对肠道同种异体移植中与排斥反应和 GVHD 相关的免疫途径的新见解导致了治疗方法从广泛的免疫抑制演变为更具针对性的策略,这些策略有望降低感染、排斥反应和 GVHD 的发病率。这些应该是进一步研究的重点,以促进其广泛应用。