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Updated: Aug 4, 2026
Mouse Models for Graft Arteriosclerosis
Published on: May 14, 2013
Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy
Luise Holzhauser1, Kevin J Clerkin2, Takeo Fujino1
1Department of Cardiology, University of Chicago, Chicago, IL, USA.
Insights
Donor-derived cell-free DNA (dd-cfDNA) is associated with cardiac allograft vasculopathy (CAV) in stable heart transplant recipients. Higher dd-cfDNA levels indicate a greater likelihood of CAV, suggesting its potential role in monitoring transplant health.
Area of Science:
- Transplantation immunology
- Molecular diagnostics
- Cardiovascular research
Background:
- Cardiac allograft vasculopathy (CAV) is a major cause of heart transplant failure.
- The utility of donor-derived cell-free DNA (dd-cfDNA) for CAV screening remains unclear.
- This study investigates the correlation between dd-cfDNA and CAV in stable heart transplant (HT) recipients.
Purpose of the Study:
- To determine if dd-cfDNA levels correlate with the presence of CAV in stable HT recipients.
- To explore the relationship between dd-cfDNA, inflammation, and angiogenesis markers.
- To assess the potential of dd-cfDNA as a non-invasive biomarker for CAV.
Main Methods:
- Sixty-five stable HT recipients (≥2 years post-transplant) were stratified based on dd-cfDNA levels (<0.12% vs. ≥0.12%).
- dd-cfDNA was quantified using a targeted amplification, next-generation sequencing assay (AlloSure®).
- Peripheral blood inflammatory and angiogenesis markers were measured via multiplex immunoassay.
Main Results:
- CAV was diagnosed in 63% of patients with high dd-cfDNA versus 35% with low dd-cfDNA (p=0.047).
- Donor-specific antibodies were more prevalent in the high dd-cfDNA group (25% vs. 3.8%, p=0.03).
- No significant differences were observed in rejection episodes, inflammatory, or angiogenesis markers between groups.
Conclusions:
- Elevated dd-cfDNA levels are associated with the presence of CAV in stable HT recipients.
- dd-cfDNA may serve as a valuable biomarker for detecting CAV.
- Further research is needed to evaluate dd-cfDNA's role in predicting CAV progression and severity.
Background:
The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients.
Methods:
Sixty-five HT recipients ≥2 years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure® ; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex® ).
Results:
Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p = .047). Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p = .03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant.
Conclusions:
Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.
