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Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
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Cell-Free DNA to Detect Heart Allograft Acute Rejection
Sean Agbor-Enoh1,2,3, Palak Shah1,4, Ilker Tunc1,2
1Genomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Circulation
|January 13, 2021
Summary
A new blood test measuring percent donor-derived cell-free DNA (%ddcfDNA) effectively detects acute rejection (AR) after heart transplantation, offering earlier diagnosis than traditional biopsies.
Area of Science:
- Transplant medicine
- Molecular diagnostics
- Immunology
Background:
- Endomyocardial biopsy (EMBx) is the standard for monitoring heart transplant recipients for acute rejection (AR).
- EMBx is invasive and has interpretation limitations.
- A sensitive blood biomarker, percent donor-derived cell-free DNA (%ddcfDNA), is explored for AR detection.
Purpose of the Study:
- To validate the performance of %ddcfDNA for detecting AR in cardiac transplant recipients.
- To compare %ddcfDNA levels in patients with AR (ACR and AMR) versus controls.
- To assess the potential of %ddcfDNA to reduce the need for EMBx.
Main Methods:
- A multicenter, prospective cohort study involving heart transplant recipients.
- Plasma samples collected contemporaneously with EMBx for %ddcfDNA measurement via shotgun sequencing.
- Histopathology data used to define AR, ACR, AMR, and controls; receiver-operator characteristic analysis performed.
Main Results:
- %ddcfDNA levels increased significantly in AR patients compared to controls (0.38% vs. 0.03%, P<0.001).
- Elevated %ddcfDNA detected ACR and AMR 0.5 and 3.2 months earlier than EMBx.
- A %ddcfDNA threshold of 0.25% showed a 99% negative predictive value for AR, potentially eliminating 81% of EMBx.
Conclusions:
- %ddcfDNA is a highly accurate biomarker for detecting AR in heart transplant recipients.
- This blood test enables earlier detection of both ACR and AMR compared to EMBx.
- %ddcfDNA monitoring shows promise for clinical utility, potentially reducing invasive procedures.
