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Transplant Proc. 2015 Oct;47(8):2400-3. doi: 10.1016/j.transproceed.2015.08.035.

Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation.

Author information

1
Chronix Biomedical, University Medical Center, Göttingen, Germany.
2
Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany.
3
Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
4
Clinic for Nephrology and Transplantation Centre, Klinikum Stuttgart, Stuttgart, Germany.
5
Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
6
Central Institute for Clinical Chemistry and Laboratory Medicine, Klinikum Stuttgart, Germany.
7
Chronix Biomedical, University Medical Center, Göttingen, Germany. Electronic address: esc@chronixbiomedical.de.

Abstract

BACKGROUND:

In solid organ transplantation, sensitive real-time biomarkers to assess the graft health are desirable to enable early intervention, for example, to avoid full-blown rejections. During rejection, high amounts of graft-derived cell-free DNA (GcfDNA) are shed into the blood stream. The quantification of this GcfDNA in allotransplantation is considered to fulfill this need, because it can be measured with great precision and at reasonable cost.

PATIENTS AND METHODS:

Patients from 2 ongoing studies in kidney (KTx) and heart (HTx) transplantation were monitored blinded on a scheduled basis, by means of a published universal droplet digital polymerase chain reaction to quantify the GcfDNA.

RESULTS:

Immediately after engraftment, GcfDNA reaches high values (>5% of total cfDNA), with a rapid decrease to values of <0.5% within 1 week. Living-related KTx recipients show lower initial values, reflecting the absence of preservation injury. Episodes of rejection in KTx and HTx are accompanied by a significant increase of GcfDNA (>5-fold) above values in patients without complications, occurring earlier than clinical or biochemical hints to rejection. One case of rejection, which became clinically suspect after 1 year and was proven with biopsy, showed a significant 10-fold increase 3 months earlier.

CONCLUSIONS:

The quantification of GcfDNA has the potential to detect rejection episodes at early stages, when other means of diagnosis are not effective. The method's noninvasiveness enables the monitoring recipients at intervals that are desired to catch rejections at early actionable stages to prevent full-blown rejection. This biomarker will be particularly valuable in regimens to minimize immunosuppression.

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