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Updated: May 5, 2026
Measurement of Antibody Effects on Cellular Function of Isolated Cardiomyocytes
Published on: March 8, 2013
Donor-Derived Cell-Free DNA in Antibody-Mediated Rejection: An Analysis of the Surveillance HeartCare Outcomes
Paul J Kim1, Amit H Alam2, Jeffrey J Teuteberg3
1Department of Medicine, University of California-San Diego, La Jolla, California, USA.
Insights
Donor-derived cell-free DNA (dd-cfDNA) shows variable accuracy for detecting antibody-mediated rejection (AMR) in heart transplant recipients. dd-cfDNA utility depends on clinical context, potentially reducing the need for routine surveillance biopsies.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biomarker Discovery
Background:
- Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for antibody-mediated rejection (AMR) after heart transplantation.
- Limited data exist on dd-cfDNA performance in a large, contemporary heart transplant cohort.
Purpose of the Study:
- To determine the incidence and timing of biopsy-proven AMR in heart transplant recipients.
- To evaluate the diagnostic performance of dd-cfDNA for detecting AMR in various clinical scenarios.
Main Methods:
- Analysis of 2,240 heart transplant recipients from the SHORE registry (2017-2022).
- Inclusion of data on biopsy results, dd-cfDNA levels, echocardiography, and donor-specific antibodies (DSA).
- Assessment of dd-cfDNA performance characteristics for AMR detection across different clinical contexts.
Main Results:
- AMR incidence varied significantly by clinical context (1.1% to 20.4%).
- dd-cfDNA levels correlated with AMR risk, especially in the presence of DSA and graft dysfunction.
- Specific dd-cfDNA thresholds (<0.20%, 0.20-0.49%, ≥0.50%) showed differential AMR incidence.
Conclusions:
- AMR incidence and dd-cfDNA utility are highly context-dependent.
- dd-cfDNA performance complements gene expression profiling for rejection monitoring.
- Findings may reduce the necessity for routine surveillance biopsies in heart transplant patients.
Background:
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a biomarker for antibody-mediated rejection (AMR), but its performance characteristics have not been evaluated in a large contemporary heart transplant population.
Objectives:
The study aimed to characterize the incidence and timing of biopsy-proven AMR and evaluate the performance characteristics of dd-cfDNA for AMR.
Methods:
The authors included 2,240 subjects from the SHORE (Surveillance HeartCare Outcomes Registry) registry transplanted between 2017 and 2022 with verified biopsy, dd-cfDNA, echocardiographic, and donor-specific antibody (DSA) data. They evaluated the performance characteristics of dd-cfDNA for AMR and the incidence of AMR in different clinical contexts.
Results:
AMR was present in 2.6% of biopsies with significant variability depending on the clinical context: AMR occurred in 1.1% of biopsies with normal graft function and no DSAs vs 20.4% of biopsies with known DSA and graft dysfunction. In patients with neither DSA nor graft dysfunction, the incidence of AMR was 0.7% for dd-cfDNA levels <0.20%, 1.2% for levels between 0.20% and 0.49%, and 6.7% for dd-cfDNA levels ≥0.50%. In patients with known DSA but no graft dysfunction, the incidence of AMR was 1.4% for dd-cfDNA levels <0.20%, 4.8% for levels between 0.20% and 0.49%, and 15.5% for dd-cfDNA levels ≥0.50%.
Conclusions:
The authors document significant context dependent variability of AMR incidence and the utility of dd-cfDNA in predicting biopsy yield. These data complement prior studies on the interpretation of peripheral gene expression profiling and dd-cfDNA for rejection monitoring and should further obviate the need for surveillance biopsies. (Surveillance HeartCare Outcomes Registry [SHORE]; NCT03695601).
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