Update on immunosuppressive strategies in intestinal transplantation.
Update on immunosuppressive strategies in intestinal transplantation.
复制标题
DOI：
10.1097/mot.0000000000000958
复制
发表时间：
2022-04-01
影响因子：
2.2
通讯作者：
Weiner J
中科院分区：
文献类型：
--
作者：
Merola J;Shamim A;Weiner J
肠是免疫学上最复杂的实体器官同种异体移植物，具有最大的排斥反应和移植物抗宿主病（GVHD）风险。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，且有经验的中心很少，因此缺乏循证、标准化和有效的治疗方案。我们在此回顾了关于免疫抑制的最新数据，重点是新的和新兴的治疗方法。最近的数据正在使该领域朝着增加使用basilixumab和考虑使用alemtuzumab进行诱导和纳入mTOR抑制剂和抗代谢药进行维持的方向发展。对于排斥反应，我们强调了TNFα抑制、α4β7整联蛋白抑制、微生物组调节、脱敏方案和耐受诱导策略的新作用。我们还强调了新兴的GVHD新疗法，特别是Janus激酶抑制的前景。对肠移植物中与排斥和GVHD相关的免疫途径的新见解已经导致治疗从广泛的免疫抑制发展到更有针对性的策略，这些策略有望降低感染，排斥和GVHD的发病率。这些应成为进一步研究的重点，以促进其广泛使用。
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 towards increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mTOR inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for TNFα 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.