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评估肾移植受者在监测和临床疑似急性排斥反应时的供体游离 DNA(dd-cfDNA)。

Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation.

机构信息

Department of Nephrology and Kidney Transplantation, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, Greece.

"Genotypos" Science Laboratory of Molecular Genetic and Cytogenetics, Athens, Greece.

出版信息

Transpl Int. 2023 Oct 13;36:11507. doi: 10.3389/ti.2023.11507. eCollection 2023.

DOI:10.3389/ti.2023.11507
PMID:37901296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10603235/
Abstract

In our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were measured at the time of biopsy and 1 month afterwards. Fourteen of 32 (43.8%) patients in the biopsy group were diagnosed with TCMR and 5 of 32 (15.6%) with ABMR. Dd-cfDNA proved to be better than creatinine in diagnosing rejection from non-rejection in patients who were biopsied. When a dd-cfDNA threshold of 0.5% was chosen, sensitivity was 73.7% and specificity was 92.3% (AUC: 0.804, 0.646-0.961). In rejection patients, levels of dd-cfDNA prior to biopsy (0.94%, 0.3-2.0) decreased substantially after initiation of treatment with median returning to baseline already at 1 month (0.33%, 0.21-0.51, = 0.0036). In the surveillance group, high levels of dd-cfDNA (>0.5%) from second month post-transplantation were correlated with non-increasing eGFR 1 year post-transplantation. The study used AlloSeq kit for kidney transplant surveillance for first time and confirmed dd-cfDNA's ability to detect rejection and monitor treatment, as well as to predict worse long-term outcomes regarding eGFR.

摘要

在我们的前瞻性、单中心队列研究中,我们收集了 30 名新接受肾移植患者的血液样本,在第 1、2、3 和 5 个月进行 dd-cfDNA 分析,同时进行肌酐/eGFR 和 DSA 监测,并收集了 32 名接受指示性活检的患者的血液样本,他们的 dd-cfDNA 水平在活检时和 1 个月后进行了测量。在活检组中,14 名患者(43.8%)被诊断为 TCMR,5 名患者(15.6%)被诊断为 ABMR。dd-cfDNA 在诊断活检患者的排斥反应方面优于肌酐。当选择 dd-cfDNA 阈值为 0.5%时,灵敏度为 73.7%,特异性为 92.3%(AUC:0.804,0.646-0.961)。在排斥反应患者中,活检前的 dd-cfDNA 水平(0.94%,0.3-2.0)在开始治疗后显著下降,中位数在 1 个月时已恢复到基线水平(0.33%,0.21-0.51, = 0.0036)。在监测组中,移植后第二个月的 dd-cfDNA 水平较高(>0.5%)与移植后 1 年内 eGFR 无增加相关。该研究首次在肾移植监测中使用 AlloSeq 试剂盒,证实了 dd-cfDNA 检测排斥反应、监测治疗以及预测 eGFR 长期预后较差的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/be3ee6cb4ec2/ti-36-11507-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/1ba49e834e60/ti-36-11507-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/0a60e9f705af/ti-36-11507-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/7fad588645ba/ti-36-11507-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/be3ee6cb4ec2/ti-36-11507-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/1ba49e834e60/ti-36-11507-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/0a60e9f705af/ti-36-11507-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/7fad588645ba/ti-36-11507-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858a/10603235/be3ee6cb4ec2/ti-36-11507-g004.jpg

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本文引用的文献

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The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients.国际心肺移植学会(ISHLT)心脏移植受者护理指南。
J Heart Lung Transplant. 2023 May;42(5):e1-e141. doi: 10.1016/j.healun.2022.10.015. Epub 2022 Dec 20.
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Comparison of methods for donor-derived cell-free DNA quantification in plasma and urine from solid organ transplant recipients.实体器官移植受者血浆和尿液中供体来源游离DNA定量方法的比较。
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Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose.
供者来源的无细胞 DNA 可预测肾移植受者的移植物排斥和严重的微血管炎症。
Front Immunol. 2024 Jul 9;15:1433918. doi: 10.3389/fimmu.2024.1433918. eCollection 2024.
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Donor-Derived Cell-Free DNA: Attractive Biomarker Seeks a Context of Use.供体来源的游离DNA:颇具吸引力的生物标志物探寻应用场景。
Transpl Int. 2023 Dec 1;36:12406. doi: 10.3389/ti.2023.12406. eCollection 2023.
短时间停用吗替麦考酚酯后和追加一剂疫苗接种后 1 和 3 个月时,既往无应答肾移植受者对 COVID-19 mRNA 疫苗接种的免疫应答。
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Transplant Proc. 2023 Jan-Feb;55(1):93-97. doi: 10.1016/j.transproceed.2022.12.003. Epub 2022 Dec 29.
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Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Kidney Transplant Rejection: Effect on Donor-derived Cell-free DNA and C-X-C Motif Chemokine Ligand 10.抗白细胞介素-6抗体克拉扎珠单抗在抗体介导的肾移植排斥反应中的作用:对供体来源的游离DNA和C-X-C基序趋化因子配体10的影响
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Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation.一组移植后长期随访受者肾移植失败的原因
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J Am Soc Nephrol. 2022 Feb;33(2):387-400. doi: 10.1681/ASN.2021091191. Epub 2022 Jan 20.