PDF(Pubmed)
Abstract：
Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data and evaluate associations between AMR and graft outcome. The present paper was developed following a Broad Scientific Advice request from the European Society for Organ Transplantation (ESOT) to the European Medicines Agency (EMA), which explored whether updating guidelines on clinical trial endpoints would encourage innovations in kidney transplantation research. ESOT considers that an AMR diagnosis must be based on a combination of histopathological factors and presence of donor-specific HLA antibodies in the recipient. Evidence for associations between individual features of AMR and impaired graft outcome is noted for microvascular inflammation scores ≥2 and glomerular basement membrane splitting of >10% of the entire tuft in the most severely affected glomerulus. Together, these should form the basis for AMR-related endpoints in clinical trials of kidney transplantation, although modifications and restrictions to the Banff diagnostic definition of AMR are proposed for this purpose. The EMA provided recommendations based on this Broad Scientific Advice request in December 2020; further discussion, and consensus on the restricted definition of the AMR endpoint, is required.
摘要：
抗体介导的排斥(AMR)是由识别供体人类白细胞抗原(HLA)或其他靶标的抗体引起的。随着AMR病理生理学知识的增加，需要综合因素来确认诊断和表型。然而,对AMR定义的频繁修改使得难以比较数据和评估AMR与移植物结局之间的关联.本文是根据欧洲器官移植学会（ESOT）向欧洲药品管理局（EMA）提出的广泛的科学建议要求而开发的，该研究探讨了更新临床试验终点指南是否会鼓励肾移植研究的创新.ESOT认为AMR诊断必须基于组织病理学因素和受体中供体特异性HLA抗体的存在的组合。在受影响最严重的肾小球中，微血管炎症评分≥2且肾小球基底膜分裂>10％的整个毛簇，注意到AMR的个体特征与移植物结局受损之间存在关联的证据。一起,这些应该成为肾移植临床试验中AMR相关终点的基础，尽管为此提出了对AMR的Banff诊断定义的修改和限制。EMA在2020年12月根据这一广泛的科学建议请求提供了建议；进一步讨论，并就AMR终点的限制性定义达成共识，是必需的。
