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临床实践中基于系统活检的转录组学与抗体介导的肾移植排斥反应诊断

Systematic Biopsy-Based Transcriptomics and Diagnosis of Antibody-Mediated Kidney Transplant Rejection in Clinical Practice.

作者信息

Dandonneau Jeanne, François Arnaud, Bertrand Dominique, Candon Sophie, de Nattes Tristan

机构信息

Univ Rouen Normandie, INSERM U1234, Rouen, France.

CHU Rouen, Pathology Department, F-76000 Rouen, France.

出版信息

Clin J Am Soc Nephrol. 2024 Sep 1;19(9):1169-1179. doi: 10.2215/CJN.0000000000000490. Epub 2024 Jul 16.

DOI:10.2215/CJN.0000000000000490
PMID:39012712
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11390017/
Abstract

KEY POINTS

Impact of biopsy-based transcriptomics in clinical practice is still unclear. Biopsy-based transcriptomics is indicated in a significant proportion of kidney transplant biopsies for the diagnosis of antibody-mediated rejection. Biopsy-based transcriptomics is useful for antibody-mediated rejection diagnosis in clinical practice.

BACKGROUND

To diagnose kidney transplant antibody-mediated rejection (AMR), biopsy-based transcriptomics can substitute for some histological criteria according to the Banff classification. However, clinical accessibility of these assays is still limited. Here, we aimed to evaluate the impact of integrating a routine-compatible molecular assay for the diagnosis of AMR in clinical practice.

METHODS

All biopsies performed in our center between 2013 and 2017 were retrospectively included. These biopsies were classified into three groups: AMR biopsies which displayed the full Banff criteria of AMR independently of biopsy-based transcriptomics; undetermined for AMR biopsies which did not meet AMR histological criteria, but would have been considered as AMR if biopsy-based transcriptomics had been positive; and control biopsies which showed no features of rejection.

RESULTS

Within the inclusion period, 342 biopsies had a complete Banff scoring. Thirty-six of the biopsies already met AMR criteria, and 43 of 306 (14%) were considered as undetermined for AMR. Among these biopsies, 24 of 43 (56%) had a molecular signature of AMR, reclassifying them into the AMR category. Five-year death-censored survival of these biopsies was unfavorable and statistically equivalent to that of the AMR category ( = 0.22), with 15 of 24 (63%) graft loss.

CONCLUSIONS

A significant proportion of biopsies could benefit from a biopsy-based transcriptomics for AMR diagnosis according to the Banff classification. Using a routine-compatible molecular tool, more than the half of these biopsies were reclassified as AMR and associated with poor allograft survival.

摘要

关键点

基于活检的转录组学在临床实践中的影响仍不明确。在相当一部分肾移植活检中,基于活检的转录组学可用于诊断抗体介导的排斥反应。基于活检的转录组学在临床实践中对抗体介导的排斥反应诊断有用。

背景

为诊断肾移植抗体介导的排斥反应(AMR),基于活检的转录组学可根据班夫分类替代一些组织学标准。然而,这些检测方法在临床上的可及性仍然有限。在此,我们旨在评估在临床实践中整合一种常规兼容分子检测方法对AMR诊断的影响。

方法

回顾性纳入2013年至2017年在我们中心进行的所有活检。这些活检分为三组:独立于基于活检的转录组学显示完整班夫AMR标准的AMR活检;不符合AMR组织学标准但如果基于活检的转录组学呈阳性则会被视为AMR的AMR未确定活检;以及未显示排斥特征的对照活检。

结果

在纳入期内,342例活检有完整的班夫评分。其中36例活检已符合AMR标准,306例中的43例(14%)被视为AMR未确定。在这些活检中,43例中的24例(56%)有AMR分子特征,将它们重新分类为AMR类别。这些活检的五年死亡校正生存率不佳,且在统计学上与AMR类别相当(P = 0.22),24例中有15例(63%)移植肾丢失。

结论

根据班夫分类,相当一部分活检可受益于基于活检的转录组学进行AMR诊断。使用一种常规兼容分子工具,这些活检中有超过一半被重新分类为AMR,且与移植肾存活率低相关。

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本文引用的文献

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Biopsy-based transcriptomics in the diagnosis of kidney transplant rejection.基于活检的转录组学在肾移植排斥诊断中的应用。
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