Nav: Home

New non-invasive assay may improve surveillance of heart and other solid-organ transplants

October 10, 2016

Philadelphia, PA, Oct. 10, 2016 - Patients who have received a solid organ transplant require lifelong immunosuppressive therapy. The threat of transplant rejection due to insufficient drug therapy must be balanced against increased risks of infections and cancer from excessive immunosuppression. A significant unmet need exists for non-invasive diagnostic tools to monitor transplant recipients, especially for early detection of active injury and rejection. A report in The Journal of Molecular Diagnostics describes a new non-invasive test that measures donor-derived cell-free DNA (dd-cfDNA) in plasma that has the potential to reduce complications and rejection, improving outcomes in transplant recipients.

"dd-cfDNA is an emerging biomarker of transplanted organ injury, and the availability of a clinical-grade, analytically validated assay is critical for advancement of this biomarker toward improving the outcomes of transplant patients," explained lead investigator Marica Grskovic, PhD, Associate Director, R&D, CareDx, Inc. (Brisbane, CA).

Plasma cfDNA has been proposed as a biomarker for prenatal testing, cancer, and organ transplantation. Taking advantage of genetic differences between a transplant donor and recipient, techniques have been developed to measure levels of a donor's DNA in the recipient's plasma, serum, or urine as a way to monitor the health of transplanted tissue, whether from the heart, lungs, liver, or other organs.

Although dd-cfDNA assays for research have been described previously, this is the first time a clinical-grade assay has been reported. The new assay detects plasma dd-cfDNA within the range of levels evident from transplant patient samples.

An advantage of the new next-generation sequencing (NGS)-based amplification assay is that it does not require determination of the donor's and recipient's genotype, a process which requires significant time, cost, and tissue availability. Although tissue biopsy is another way to monitor a transplanted organ, it is invasive, time consuming, costly, and risky. The new assay can be completed within three days, which can be important for clinical decision-making.

In the current report, data are presented from a multi-center heart transplantation study showing that dd-cfDNA was, on average, three-fold higher in patients experiencing acute rejection than in stable transplant recipients without acute rejection. A decrease in dd-cfDNA levels upon successful anti-rejection treatment was also observed.

Hannah Valantine, MD, Senior Investigator NHLBI, and NIH Chief Officer for Scientific Workforce Diversity, stated, "In collaboration with colleagues Drs. Stephen Quake, Kiran Khush, and Iwijn De Vlaminck at Stanford, we performed the pioneering research studies using NGS for heart and lung transplant. I am delighted to see this technology translating into a clinical-grade assay to which patients will have access to improve the precision of patient management."

The researchers expect the assay to be useful for monitoring other types of transplanted organs. Additional multi-centered observational studies for heart and kidney transplant patients are underway to further evaluate the assay's clinical validity and utility. The assay is currently validated only for single organ donor/recipient pairs.

"These results show promise in using cfDNA not only to detect rejection, but also to monitor response to treatment. The ongoing measurement of cfDNA may allow clinicians to better personalize care, adjust immunosuppression regimens, and improve the long-term outcomes of transplant recipients," noted Dr. Grskovic.
-end-


Elsevier Health Sciences

Related Dna Articles:

A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
Switching DNA and RNA on and off
DNA and RNA are naturally polarised molecules. Scientists believe that these molecules have an in-built polarity that can be reoriented or reversed fully or in part under an electric field.
New DNA synthesis technique promises rapid, high-fidelity DNA printing
Today, DNA is synthesized as an organic chemist would, using toxic chemicals and error-prone steps that limit accuracy and thus length to about 200 base pairs.
The changing shape of DNA
The shape of DNA can be changed with a range of triggers including copper and oxygen - according to new research from the University of East Anglia.
More Dna News and Dna Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.