A novel INDEL-based next-generation sequencing assay for monitoring donor-derived cell-free DNA in renal transplant recipients—from bedside to results: a UK pilot study
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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: 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.
DOI: 10.4285/ctr.25.0004
Authors: George E. Nita, Fotini Partheniou, Dan Ridgway, Sanjay Mehra, Matthew Howse, Abdul Hammad, Andrew R. Jones, Petra M. Goldsmith
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4409780599