Editors' ChoiceHeart Transplantation

Blood Sample Supplants Biopsy?

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Science Translational Medicine  27 Apr 2011:
Vol. 3, Issue 80, pp. 80ec59
DOI: 10.1126/scitranslmed.3002539

Although singer Janis Joplin begged her beloved to take another little piece of her heart, most cardiac transplantation patients are reluctant to donate a slice of theirs. Currently, these patients have no choice—endomyocardial biopsy is the standard of care for monitoring acute allograft rejection after cardiac transplantation. This costly procedure is associated with substantial patient discomfort and rare but potentially lethal complications. Now, Snyder and colleagues demonstrate that screening for donor DNA in organ recipients may serve as an effective biopsy surrogate.

First, the authors performed a digital polymerase chain reaction (PCR) procedure on circulating cell-free DNA isolated from the serum of 39 female patients who received hearts from male donors using probes for the Y chromosome—which is present only in males. Some of these patients had biopsy-documented organ rejection, whereas others did not. Snyder et al. found that when 2% or more of the circulating DNA in recipients was donor DNA, more than 75% of these individuals could be correctly classified as having acute cellular rejection. Next, the authors expanded their clinical population beyond females who received organs from male donors to an additional 44 male and female patients and genotyped more than 150,000 single-nucleotide polymorphisms (SNPs) on a standard genotyping array. Using previously acquired donor and recipient genetic information, they deduced that searching for specific homozygous donor SNPs in the organ recipient’s whole blood correctly identified 83% of biopsy-confirmed allograft rejection events. The researchers also noted that elevated amounts of donor DNA were detectable weeks and at times months before biopsy confirmation of rejection. These observations indicate that cell-free circulating DNA could facilitate the early implementation of organ-saving immunosuppressive therapy in those at risk.

These findings provide remarkable proof-of-principle data for the use of blood-based diagnostics in all forms of organ transplantation. Although prospective clinical trials are still required for validation of the current findings, it is likely that the use of blood-based diagnostics in the assessment of solid-organ transplant rejection will mean that giving up a piece of one’s heart remains a personal decision.

T. M. Snyder et al., Universal noninvasive detection of solid organ transplant rejection. Proc. Natl. Acad. Sci. U.S.A. 108, 6229–6234 (2011). [Abstract]

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