{"title":"补体疗法在实体器官移植中的前景。","authors":"Justin A Steggerda, Peter S Heeger","doi":"10.1097/TP.0000000000004927","DOIUrl":null,"url":null,"abstract":"<p><p>Transplantation is the ideal therapy for end-stage organ failure, but outcomes for all transplant organs are suboptimal, underscoring the need to develop novel approaches to improve graft survival and function. The complement system, traditionally considered a component of innate immunity, is now known to broadly control inflammation and crucially contribute to induction and function of adaptive T-cell and B-cell immune responses, including those induced by alloantigens. Interest of pharmaceutical industries in complement therapeutics for nontransplant indications and the understanding that the complement system contributes to solid organ transplantation injury through multiple mechanisms raise the possibility that targeting specific complement components could improve transplant outcomes and patient health. Here, we provide an overview of complement biology and review the roles and mechanisms through which the complement system is pathogenically linked to solid organ transplant injury. We then discuss how this knowledge has been translated into novel therapeutic strategies to improve organ transplant outcomes and identify areas for future investigation. Although the clinical application of complement-targeted therapies in transplantation remains in its infancy, the increasing availability of new agents in this arena provides a rich environment for potentially transformative translational transplant research.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Promise of Complement Therapeutics in Solid Organ Transplantation.\",\"authors\":\"Justin A Steggerda, Peter S Heeger\",\"doi\":\"10.1097/TP.0000000000004927\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Transplantation is the ideal therapy for end-stage organ failure, but outcomes for all transplant organs are suboptimal, underscoring the need to develop novel approaches to improve graft survival and function. The complement system, traditionally considered a component of innate immunity, is now known to broadly control inflammation and crucially contribute to induction and function of adaptive T-cell and B-cell immune responses, including those induced by alloantigens. Interest of pharmaceutical industries in complement therapeutics for nontransplant indications and the understanding that the complement system contributes to solid organ transplantation injury through multiple mechanisms raise the possibility that targeting specific complement components could improve transplant outcomes and patient health. Here, we provide an overview of complement biology and review the roles and mechanisms through which the complement system is pathogenically linked to solid organ transplant injury. We then discuss how this knowledge has been translated into novel therapeutic strategies to improve organ transplant outcomes and identify areas for future investigation. Although the clinical application of complement-targeted therapies in transplantation remains in its infancy, the increasing availability of new agents in this arena provides a rich environment for potentially transformative translational transplant research.</p>\",\"PeriodicalId\":23316,\"journal\":{\"name\":\"Transplantation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/TP.0000000000004927\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/TP.0000000000004927","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
移植是治疗终末期器官衰竭的理想疗法,但所有移植器官的治疗效果都不理想,这突出表明需要开发新的方法来提高移植器官的存活率和功能。补体系统传统上被认为是先天性免疫的一个组成部分,但现在人们已经知道它能广泛控制炎症,并对诱导适应性 T 细胞和 B 细胞免疫反应(包括由异体抗原诱导的免疫反应)和发挥其功能起着至关重要的作用。制药业对用于非移植适应症的补体治疗药物很感兴趣,而且人们认识到补体系统通过多种机制造成了实体器官移植损伤,这就为靶向特定补体成分改善移植结果和患者健康提供了可能性。在此,我们将概述补体生物学,并回顾补体系统与实体器官移植损伤在病理上相关的作用和机制。然后,我们将讨论如何将这些知识转化为改善器官移植预后的新型治疗策略,并确定未来的研究领域。尽管补体靶向疗法在移植中的临床应用仍处于起步阶段,但这一领域中越来越多的新药物为潜在的变革性移植转化研究提供了丰富的环境。
The Promise of Complement Therapeutics in Solid Organ Transplantation.
Transplantation is the ideal therapy for end-stage organ failure, but outcomes for all transplant organs are suboptimal, underscoring the need to develop novel approaches to improve graft survival and function. The complement system, traditionally considered a component of innate immunity, is now known to broadly control inflammation and crucially contribute to induction and function of adaptive T-cell and B-cell immune responses, including those induced by alloantigens. Interest of pharmaceutical industries in complement therapeutics for nontransplant indications and the understanding that the complement system contributes to solid organ transplantation injury through multiple mechanisms raise the possibility that targeting specific complement components could improve transplant outcomes and patient health. Here, we provide an overview of complement biology and review the roles and mechanisms through which the complement system is pathogenically linked to solid organ transplant injury. We then discuss how this knowledge has been translated into novel therapeutic strategies to improve organ transplant outcomes and identify areas for future investigation. Although the clinical application of complement-targeted therapies in transplantation remains in its infancy, the increasing availability of new agents in this arena provides a rich environment for potentially transformative translational transplant research.
期刊介绍:
The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year.
Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal.
Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed.
The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.