Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Transpl Int. 2020 Jan;33(1):41-49. doi: 10.1111/tri.13487. Epub 2019 Aug 27.
Chronic lung allograft dysfunction (CLAD) comprises both bronchiolitis obliterans syndrome and restrictive allograft syndrome as subtypes. After lung transplantation, CLAD remains a major limitation for long-term survival, and lung transplant recipients therefore have poorer outcomes compared with recipients of other solid organ transplants. Although the number of lung transplants continues to increase globally, the field demands detailed understanding of immunoregulatory mechanisms and more effective individualized therapies to combat CLAD. Emerging evidence suggests that CLAD is multifactorial and involves a complex, delicate interplay of multiple factors, including perioperative donor characteristics, inflammation induced immediately following transplant, post-transplant infection and interplay between allo- and autoimmunity directed to donor antigens. Recently, identification of stress-induced exosome release from the transplanted organ has emerged as an underlying mechanism in the development of chronic rejection and promises to prompt novel strategies for future therapeutic interventions. In this review, we will discuss recent studies and ongoing research into the mechanisms for the development of CLAD, with emphasis on immune responses to lung-associated self-antigens-that is, autoimmunity.
慢性肺移植功能障碍（CLAD）包括细支气管炎闭塞综合征和限制性移植物综合征两种亚型。肺移植后，CLAD 仍然是长期生存的主要限制因素，与其他实体器官移植受者相比，肺移植受者的预后更差。尽管全球肺移植数量持续增加，但该领域需要详细了解免疫调节机制，并开发更有效的个体化治疗方法来对抗 CLAD。新出现的证据表明，CLAD 是多因素的，涉及多种因素的复杂、微妙相互作用，包括围手术期供体特征、移植后立即发生的炎症、移植后感染以及同种异体和自身免疫对供体抗原的相互作用。最近，从移植器官中释放应激诱导的外泌体被确定为慢性排斥反应发展的潜在机制，并有望为未来的治疗干预措施提供新的策略。在这篇综述中，我们将讨论 CLAD 发展机制的最新研究和正在进行的研究，重点是对肺相关自身抗原（即自身免疫）的免疫反应。
