Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection

Study Questions:

Can circulating donor DNA be used to monitor rejection of heart transplants?


This was a prospective cohort study of 65 patients (565 samples) that tested the utility of cell-free donor-derived DNA (cfdDNA) in diagnosing acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (depth = 1.2 gigabase pairs) to quantify the fraction of cfdDNA.


Compared to endomyocardial biopsy results, cfdDNA provided a diagnosis of acute rejection after heart transplantation with an area under the receiver operating characteristic curve of 0.83, and sensitivity and specificity comparable to the intrinsic performance of the biopsy itself.


The authors concluded that this noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health.


Routine surveillance for transplant rejection is required following cardiac transplantation so that appropriate therapies can be provided when necessary. The current gold standard for diagnosis of rejection is endomyocardial biopsy, which is an invasive procedure associated with risk, discomfort, and expense. This study provides validation of a previous retrospective study that demonstrated increased levels of donor DNA correlated with acute cellular rejection, as determined by endomyocardial biopsy. This method may have utility for monitoring the status of other solid organ transplants as well. Since this is a quantitative measure, threshold values may need to be determined for individual patients to optimize sensitivity and specificity. Further validation of this technique is warranted.

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