Prospective evaluation of donor-derived cell-free DNA for noninvasive detection of acute rejection in an Asian heart transplant population.
- 1Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract
Endomyocardial biopsy (EMB) is the gold standard for diagnosing post-heart transplant acute rejection (AR) but is invasive. Donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker, yet thresholds for Asian recipients remain undefined. This prospective study enrolled 80 patients, with 299 dd-cfDNA specimens analyzed via a novel Chinese-developed next-generation sequencing assay targeting 48 Indel sites. A reference cohort (n = 42) established post-transplant dd-cfDNA kinetics, while a biopsy cohort (n = 41, 18 acute cellular rejection [ACR], 9 antibody-mediated rejection [AMR], 14 no rejection [NR]) paired with EMB evaluated diagnostic performance. dd-cfDNA peaked at week 1, with a stable trend emerging from week 4 and stable levels reached by week 8. AR patients had significantly higher dd-cfDNA levels than NR patients (0.87% vs. 0.23%, P < 0.001). The optimal composite AR threshold was 0.33% (AUC = 0.874, sensitivity 81.0%, specificity 85.7%). dd-cfDNA decreased post-therapy (P = 0.011) and showed an inverse association with left ventricular ejection fraction (LVEF) (P = 0.004). This study provides initial evidence for an assay- and cohort-specific dd-cfDNA threshold (0.33%) for AR detection in Chinese recipients. Given the modest NPV (75.0%), this threshold is better suited for a "rule-in" strategy, and low values should not be used in isolation to defer biopsy. External validation in multicenter cohorts is required before routine clinical implementation.
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BibTeX
@article{zheng2026prospective,
title = {{Prospective evaluation of donor-derived cell-free DNA for noninvasive detection of acute rejection in an Asian heart transplant population.}},
author = {Shanshan Zheng and Sheng Liu and Zhiyuan Zhu and Jie Huang and Zhongkai Liao and Zhe Zheng and Xiaonan Fang and Lin Zhang and Hang Xu and Jiexu Ma and Yige Huyan and Xinhe Xu and Zhengbang Zou},
journal = {Transplant international : official journal of the European Society for Organ Transplantation},
year = {2026},
month = oct,
doi = {10.3389/ti.2026.16415},
url = {https://europepmc.org/article/MED/42898121},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prospective evaluation of donor-derived cell-free DNA for noninvasive detection of acute rejection in an Asian heart transplant population.
AU - Shanshan Zheng
AU - Sheng Liu
AU - Zhiyuan Zhu
AU - Jie Huang
AU - Zhongkai Liao
AU - Zhe Zheng
AU - Xiaonan Fang
AU - Lin Zhang
AU - Hang Xu
AU - Jiexu Ma
AU - Yige Huyan
AU - Xinhe Xu
AU - Zhengbang Zou
PY - 2026
DA - 2026/10/05
JO - Transplant international : official journal of the European Society for Organ Transplantation
DO - 10.3389/ti.2026.16415
UR - https://europepmc.org/article/MED/42898121
AB - Endomyocardial biopsy (EMB) is the gold standard for diagnosing post-heart transplant acute rejection (AR) but is invasive. Donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker, yet thresholds for Asian recipients remain undefined. This prospective study enrolled 80 patients, with 299 dd-cfDNA specimens analyzed via a novel Chinese-developed next-generation sequencing assay targeting 48 Indel sites. A reference cohort (n = 42) established post-transplant dd-cfDNA kinetics, while a biopsy cohort (n = 41, 18 acute cellular rejection [ACR], 9 antibody-mediated rejection [AMR], 14 no rejection [NR]) paired with EMB evaluated diagnostic performance. dd-cfDNA peaked at week 1, with a stable trend emerging from week 4 and stable levels reached by week 8. AR patients had significantly higher dd-cfDNA levels than NR patients (0.87% vs. 0.23%, P < 0.001). The optimal composite AR threshold was 0.33% (AUC = 0.874, sensitivity 81.0%, specificity 85.7%). dd-cfDNA decreased post-therapy (P = 0.011) and showed an inverse association with left ventricular ejection fraction (LVEF) (P = 0.004). This study provides initial evidence for an assay- and cohort-specific dd-cfDNA threshold (0.33%) for AR detection in Chinese recipients. Given the modest NPV (75.0%), this threshold is better suited for a "rule-in" strategy, and low values should not be used in isolation to defer biopsy. External validation in multicenter cohorts is required before routine clinical implementation.
SN - 0934-0874
SN - 1432-2277
ER -