Frontiers in Immunology (Mar 2022)
Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts
- Luying Guo,
- Luying Guo,
- Luying Guo,
- Luying Guo,
- Luying Guo,
- Jia Shen,
- Jia Shen,
- Jia Shen,
- Jia Shen,
- Jia Shen,
- Wenhua Lei,
- Wenhua Lei,
- Wenhua Lei,
- Wenhua Lei,
- Wenhua Lei,
- Pengpeng Yan,
- Pengpeng Yan,
- Pengpeng Yan,
- Pengpeng Yan,
- Pengpeng Yan,
- Meifang Wang,
- Meifang Wang,
- Meifang Wang,
- Meifang Wang,
- Meifang Wang,
- Qin Zhou,
- Qin Zhou,
- Qin Zhou,
- Qin Zhou,
- Qin Zhou,
- Huiping Wang,
- Huiping Wang,
- Huiping Wang,
- Huiping Wang,
- Huiping Wang,
- Jianyong Wu,
- Jianyong Wu,
- Jianyong Wu,
- Jianyong Wu,
- Jianyong Wu,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Rending Wang,
- Rending Wang,
- Rending Wang,
- Rending Wang,
- Rending Wang
Affiliations
- Luying Guo
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Luying Guo
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Luying Guo
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Luying Guo
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Luying Guo
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Jia Shen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jia Shen
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Jia Shen
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Jia Shen
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Jia Shen
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Wenhua Lei
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Wenhua Lei
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Wenhua Lei
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Wenhua Lei
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Wenhua Lei
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Pengpeng Yan
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Pengpeng Yan
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Pengpeng Yan
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Pengpeng Yan
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Pengpeng Yan
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Meifang Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Meifang Wang
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Meifang Wang
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Meifang Wang
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Meifang Wang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Qin Zhou
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Qin Zhou
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Qin Zhou
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Qin Zhou
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Qin Zhou
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Huiping Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Huiping Wang
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Huiping Wang
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Huiping Wang
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Huiping Wang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Jianyong Wu
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jianyong Wu
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Jianyong Wu
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Jianyong Wu
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Jianyong Wu
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jianghua Chen
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Jianghua Chen
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Jianghua Chen
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Jianghua Chen
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Rending Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Rending Wang
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- Rending Wang
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Rending Wang
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Rending Wang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2022.796326
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
