دورية أكاديمية
أعرض في EDS

Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant

التفاصيل البيبلوغرافية
العنوان: Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant
المؤلفون: Justin P. Rosenheck, DO, David J. Ross, MD, Mena Botros, MD, Alexander Wong, MD, Jonathan Sternberg, PhD, Yen-An Chen, MS, Nathan Liang, BA, Amy Baer, MS, Ebad Ahmed, PhD, Ryan Swenerton, PhD, Bernhard G. Zimmermann, PhD, Gordon Fehringer, PhD, Zachary P. Demko, PhD, Michael Olymbios, MD, Paul R. Billings, MD, PhD, Brian C. Keller, MD, PhD
المصدر: Transplantation Direct, Vol 8, Iss 4, p e1317 (2022)
بيانات النشر: Wolters Kluwer, 2022.
سنة النشر: 2022
المجموعة: LCC:Surgery
مصطلحات موضوعية: Surgery, RD1-811
الوصف: Background. Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies. Methods. We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort. Results. The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%–2.32%, P = 5 × 10−6), AMR (2.50%, IQR: 2.06%–3.79%, P = 2 × 10−5), INFXN (0.74%, IQR: 0.46%–1.38%, P = 0.02), and CLAD/NRAD (1.60%, IQR: 0.57%–2.60%, P = 1.4 × 10−4) versus the stable cohort. Area under the receiver operator characteristic curve for AR versus stable was 0.91 (95% confidence interval [CI]: 0.83-0.98). Using a ≥1% dd-cfDNA fraction threshold, sensitivity for AR was 89.1% (95% CI: 76.2%-100.0%), specificity 82.9% (95% CI: 73.3%-92.4%), positive predictive value, 51.9% (95% CI: 37.5%-66.3%), and negative predictive value, 97.3% (95% CI: 94.3%-100%). For combined allograft injury area under the receiver operator characteristic curve was 0.76 (95% CI: 0.66-0.85), sensitivity 59.9% (95% CI: 46.0%-73.9%), specificity 83.9% (95% CI: 74.1%-93.7%), positive predictive value, 43.6% (95% CI: 27.6%-59.6%), and negative predictive value, 91.0% (95% CI: 87.9%-94.0%). Conclusions. These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2373-8731
00000000
Relation: http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001317; https://doaj.org/toc/2373-8731
DOI: 10.1097/TXD.0000000000001317
URL الوصول: https://doaj.org/article/9edea27d61424d5caf9b33424f5d3cb2
رقم الأكسشن: edsdoj.9edea27d61424d5caf9b33424f5d3cb2
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23738731
00000000
DOI:10.1097/TXD.0000000000001317