Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts.
Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts.
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血浆供体来源的游离 DNA 水平与肾同种异体移植物中的炎症负担和巨噬细胞胞外陷阱活性相关
DOI：
10.3389/fimmu.2022.796326
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Guo L;Shen J;Lei W;Yan P;Wang M;Zhou Q;Wang H;Wu J;Chen J;Wang R
最近的研究证实，血浆供体来源的无细胞DNA(DdcfDNA)是肾移植后移植肾损伤的可靠的非侵入性生物标志物。然而，受体之间血浆ddcfDNA水平的差异限制了它们的临床应用。本研究旨在通过研究肾移植受者Banff病变和炎性浸润物对ddcfDNA水平的影响，探讨与血浆ddcfDNA升高相关的内在因素。从2017年3月至2019年9月，共纳入106例肾移植患者，其中正常/非特异性变化13例，交界性变化13例，T细胞介导的排斥反应60例，抗体介导的排斥反应20例。根据Banff 2017标准，由两名经验丰富的病理学家进行组织学分类。血浆ddcfDNA组分为0.12%~10.22%，中位数为0.91%。肾小球炎症、内膜动脉炎和严重间质炎症等Banff组织学亚组分与血浆ddcfDNA水平升高相关。用免疫组织化学方法对移植物中的炎性细胞进行表型分析，并用数字图像识别技术进行自动计数。Pearson相关分析显示，移植肾巨噬细胞浸润与血浆ddcfDNA水平呈显著正相关。此外，巨噬细胞胞外TRAP(MET)活性与血浆ddcfDNA水平的升高显著相关。结果表明，血浆ddcfDNA可反映移植肾炎症状态，提示Mets在移植肾损伤的发病机制中可能起重要作用。
Recent studies have confirmed the role of plasma donor-derived cell-free DNA (ddcfDNA) as a reliable non-invasive biomarker for allograft injury after kidney transplantation. Whereas the variability of plasma ddcfDNA levels among recipients has limited their clinical use. This study aimed to explore the intrinsic factors associated with plasma ddcfDNA elevation by investigating the impact of Banff lesions and inflammatory infiltrates on ddcfDNA levels in kidney transplant recipients. From March 2017 to September 2019, a total of 106 kidney transplant recipients with matched allograft biopsies were included, consisting of 13 recipients with normal/nonspecific changes, 13 recipients with borderline changes, 60 with T cell-mediated rejection, and 20 with antibody-mediated rejection. Histologic classification was performed according to the Banff 2017 criteria by two experienced pathologists. Plasma ddcfDNA fractions ranged from 0.12% to 10.22%, with a median level of 0.91%. Banff histology subelements including glomerulitis, intimal arteritis, and severe interstitial inflammation were correlated with increased plasma ddcfDNA levels. The inflammatory cell infiltrate in the allografts was phenotyped by immunochemistry and automatically counted by digital image recognition. Pearson correlation analysis revealed a significant positive correlation between macrophage infiltrations in allografts and plasma ddcfDNA levels. Additionally, macrophage extracellular trap (MET) activity was significantly associated with the rise in plasma ddcfDNA levels. Our findings demonstrated that plasma ddcfDNA could reflect the inflammatory state in renal allografts and suggested the potential role of METs in the pathogenesis of allograft injury.