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肺移植后发生慢性肺移植物功能障碍(CLAD)时无细胞DNA的供体片段升高,但感染性并发症期间未升高。

Donor Fractions of Cell-Free DNA Are Elevated During CLAD But Not During Infectious Complications After Lung Transplantation.

作者信息

Novo Mirza, Nordén Rickard, Westin Johan, Dellgren Göran, Böhmer Jens, Ricksten Anne, Magnusson Jesper M

机构信息

Department of Respiratory Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Transpl Int. 2024 Jul 24;37:12772. doi: 10.3389/ti.2024.12772. eCollection 2024.

DOI:10.3389/ti.2024.12772
PMID:39114640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11303165/
Abstract

During the last few years, cell-free DNA (cfDNA) has emerged as a possible non-invasive biomarker for prediction of complications after lung transplantation. We previously published a proof-of-concept study using a digital droplet polymerase chain reaction (ddPCR)-based method for detection of cfDNA. In the current study, we aimed to further evaluate the potential clinical usefulness of detecting chronic lung allograft dysfunction (CLAD) using three different ddPCR applications measuring and calculating the donor fraction (DF) of cfDNA as well as one method using the absolute amount of donor-derived cfDNA. We analyzed 246 serum samples collected from 26 lung transplant recipients. Nine of the patients had ongoing CLAD at some point during follow-up. All four methods showed statistically significant elevation of the measured variable in the CLAD samples compared to the non-CLAD samples. The results support the use of ddPCR-detected cfDNA as a potential biomarker for prediction of CLAD. These findings need to be validated in a subsequent prospective study.

摘要

在过去几年中,游离DNA(cfDNA)已成为一种可能用于预测肺移植术后并发症的非侵入性生物标志物。我们之前发表了一项概念验证研究,该研究使用基于数字液滴聚合酶链反应(ddPCR)的方法来检测cfDNA。在当前研究中,我们旨在进一步评估使用三种不同的ddPCR应用来测量和计算cfDNA的供体分数(DF)以及一种使用供体来源cfDNA绝对量的方法来检测慢性肺移植功能障碍(CLAD)的潜在临床实用性。我们分析了从26名肺移植受者收集的246份血清样本。其中9名患者在随访期间的某个时间点出现了持续性CLAD。与非CLAD样本相比,所有四种方法均显示CLAD样本中测量变量有统计学意义的升高。结果支持将ddPCR检测的cfDNA用作预测CLAD的潜在生物标志物。这些发现需要在后续的前瞻性研究中得到验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/934f/11303165/d20ca8dec1e4/ti-37-12772-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/934f/11303165/e4acd77ffb15/ti-37-12772-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/934f/11303165/d20ca8dec1e4/ti-37-12772-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/934f/11303165/e4acd77ffb15/ti-37-12772-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/934f/11303165/d20ca8dec1e4/ti-37-12772-g002.jpg

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本文引用的文献

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Transpl Int. 2023 Oct 30;36:11260. doi: 10.3389/ti.2023.11260. eCollection 2023.
2
Effect of once-per-day tacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial.在斯堪的纳维亚(ScanCLAD)肺移植后,每日一次他克莫司与每日两次环孢素对 3 年慢性肺移植物功能障碍发生率的影响:一项多中心随机对照试验。
Lancet Respir Med. 2024 Jan;12(1):34-44. doi: 10.1016/S2213-2600(23)00293-X. Epub 2023 Sep 10.
3
Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes.运动后 cfDNA 水平升高主要来源于成熟的多形核中性粒细胞,少量来源于心肌细胞。
Cell Rep Med. 2023 Jun 20;4(6):101074. doi: 10.1016/j.xcrm.2023.101074. Epub 2023 Jun 7.
4
Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis.精神疾病中循环游离DNA水平:一项系统综述与荟萃分析
Int J Mol Sci. 2023 Feb 8;24(4):3402. doi: 10.3390/ijms24043402.
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BMC Pulm Med. 2023 Jan 26;23(1):37. doi: 10.1186/s12890-022-02229-y.
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