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Background: Monitoring donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive method for assessing allograft health in renal transplant recipients. This UK pilot study evaluated a novel insertion and deletion (INDEL)-based next-generation sequencing (NGS) assay for detecting dd-cfDNA and explored its association with potentially injurious concomitant pathologies, including donor-specific antibodies. Current methods are limited to first and only transplant recipients, as other assays cannot distinguish graft injury in the context of transplantation from multiple donors.
Methods: Fourteen high-risk renal transplant recipients (level IV human leukocyte antigen mismatch, calculated reaction frequency >20%, retransplant) were recruited between October 2023 and July 2024 at Liverpool University Hospitals. Plasma samples were collected 6 months posttransplant, and cfDNA was extracted using QIAsymphony DSP Circulating DNA Kit (Qiagen). dd-cfDNA was quantified using the Devyser Accept cfDNA assay (Devyser), and NGS was performed using MiSeq (Illumina).
Results: We present preliminary observations from the first 14 patients included in this proof-of-concept arm of the study. A dd-cfDNA level ≤0.5% correlated with stable graft function (n=11). Patients with dd-cfDNA ≥1.0% had supratherapeutic tacrolimus levels (n=2). Intermediate dd-cfDNA levels (0.5%–1.0%) were found in the setting of de novo donor-specific antibody emergence (n=1). We were able to identify informative markers and derive interpretable results in a multitransplant recipient setting.
Conclusions: The INDEL-based NGS assay is a promising novel tool for detecting and monitoring dd-cfDNA in renal transplant recipients with an easy-to-implement workflow.
These preliminary results support its clinical utility in a high-immunological-risk setting. These findings are consistent with emergent literature; however, longitudinal data and further validation in a larger cohort of patients are required.*표시는 필수 입력사항입니다.
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도서위치안내: 정기간행물실(524호) / 서가번호: 국내16
2021년 이전 정기간행물은 온라인 신청(원문 구축 자료는 원문 이용)
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