T-cell Mediated Rejection Associated Microvascular Inflammation in the Allograft Kidney: RNAseq Analysis Using the Banff Human Organ Transplant Gene Panel

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2024-07-21 DOI:10.1111/ctr.15410

Adarsh Barwad, Yuchen Huang, Parmjeet Randhawa

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引用次数: 0

Abstract

Background

Microvascular inflammation (MVI) can occur in biopsies showing T-cell mediated rejection (TCMR), but it is not well established that T-cells can directly mediate microvascular injury (TCMR-MVI).

Methods

This was a cross sectional RNAseq based Banff Human Organ Transplant (BHOT) gene expression (GE) analysis. The objective of this study was to probe the molecular signature of TCMR-MVI in comparison with C4d+, DSA+ antibody mediated rejection (ABMR), stable renal function (STA), and TCMR without MVI. Transcriptome analysis utilized CLC genomic workbench and R-studio software.

Results

No gene set was specific for any diagnostic category, and all were expressed at low levels in STA biopsies. BHOT gene set scores could differentiate ABMR from TCMR and TCMR-MVI, but not TCMR from TCMR-MVI. TCMR-MVI underexpressed several genes associated with ABMR including DSATs, ENDAT, immunoglobulin genes, ADAMDEC1, PECAM1 and NK cell transcripts (MYBL1, GNLY), but overexpressed C3, NKBBIZ, and LTF. On the other hand, there was no significant difference in the expression of these genes in TCMR-MVI versus TCMR. This indicates that the GE profile of TCMR MVI aligns more closely with TCMR than ABMR. The limitations of classifying biopsies using the binary ABMR-TCMR algorithm, and the occurrence of common pathogenesis mechanisms amongst different rejection phenotype was highlighted by the frequent presence of molecular mixed rejection.

Conclusions

T-cell mediated mechanisms play a significant role in the pathogenesis of MVI. GE was broadly different between rejection phenotypes, but molecular scores varied substantially between biopsies with the same Banff grade. It was not always possible to achieve precise molecular score-based diagnostic categorization of individual patients.

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T细胞介导的异体肾排斥相关微血管炎症：利用班夫人体器官移植基因组进行RNAseq分析。

背景：微血管炎症（MVI）可发生在显示 T 细胞介导的排斥反应（TCMR）的活检组织中，但 T 细胞可直接介导微血管损伤（TCMR-MVI）的说法尚未得到充分证实：这是一项基于 RNAseq 的横断面班夫人体器官移植（BHOT）基因表达（GE）分析。本研究的目的是探究 TCMR-MVI 与 C4d+、DSA+ 抗体介导的排斥反应（ABMR）、肾功能稳定（STA）和无 MVI 的 TCMR 相比的分子特征。转录组分析采用了 CLC 基因组工作台和 R-studio 软件：结果：没有一组基因对任何诊断类别具有特异性，所有基因在 STA 活检中的表达水平都很低。BHOT基因组评分能区分ABMR与TCMR和TCMR-MVI，但不能区分TCMR与TCMR-MVI。TCMR-MVI 低表达了与 ABMR 相关的几个基因，包括 DSATs、ENDAT、免疫球蛋白基因、ADAMDEC1、PECAM1 和 NK 细胞转录本（MYBL1、GNLY），但高表达了 C3、NKBBIZ 和 LTF。另一方面，这些基因在 TCMR-MVI 与 TCMR 中的表达没有显著差异。这表明，TCMR MVI 的基因表达谱与 TCMR 更为接近，而不是 ABMR。使用ABMR-TCMR二元算法对活检进行分类的局限性，以及分子混合排斥反应的频繁出现凸显了不同排斥表型之间存在共同的发病机制：结论：T细胞介导的机制在MVI的发病机制中起着重要作用。不同排斥表型的GE大致相同，但相同Banff分级的活检组织的分子评分差异很大。对个别患者进行基于分子评分的精确诊断分类并非总是可行。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.