The findings suggest that transplant recipients who share the same pattern of genes but are still on conventional medication may be able to reduce or eliminate their lifelong dependence on immunosuppressive drugs. The study may also help physicians determine how best to induce acceptance, or tolerance, of donor organs in all transplant patients, regardless of their gene expression profiles.
"We're very excited by the findings," said Minnie Sarwal, MD, PhD, a pediatric nephrologist at Packard Children's. "Most transplant patients who stop taking their medications will reject their organ. But now we have the chance of telling someone committed to a lifetime of drugs that it may be possible to minimize their exposure to the drugs."
Although the anti-rejection medications, known as immunosuppressants, tamp down the immune system enough to permit lifesaving organ transplants, their benefits come at a price. They also quash the body's natural response to dangerous invaders, such as bacteria and viruses, and to rogue cancer cells. Transplant physicians prescribing immunosuppressants to their patients walk a fine line between avoiding organ rejection and increasing the risk of infection and cancer.
Sarwal, associate professor of pediatrics at the medical school, is the senior author of the research, which will be published Aug. 20 in the advance online edition of the Proceedings of the National Academy of Sciences. She collaborated with physicians at Stanford and Packard Children's, as well as with colleagues from the Veterans Affairs Palo Alto Health Care System and several institutions in France, China and the Netherlands.
The researchers used microarray, or gene chip, technology to compare gene expression patterns in blood samples from 16 healthy volunteers with those from three groups of adult kidney transplant recipients from the United States, Canada and France: 22 people on anti-rejection medications who had healthy donor kidneys, 36 people who were taking their medications but who were still rejecting their organs and 17 "tolerant" people who had successfully stopped taking their medications without rejecting their donated kidneys.
Sarwal and her collaborators found that the expression pattern of just 33 genes in a random sampling of peripheral blood could be used to accurately pick out more than 90 percent of the tolerant patients. What's more, one out of 12 stable, fully medicated patients and five out of 10 patients on a modified, low-dose immunosuppressant regimen shared very similar expression patterns.
The findings imply that patients regularly taking immunosuppressants who have a strong matching pattern for the tolerance genes may be able to safely reduce or even eliminate their dependence on the medication. Equally important, it suggests that patients who don't share the gene pattern, even if on very low-dose medication, should be particularly vigilant about continuing to take their immunosuppressants.
"For the first time, we now have evidence that will help us say to the five out of 10 patients without this expression pattern, 'Please, please don't think about changing your medications'," said Sarwal. "At the same time, we may be able to say a different patient, 'We'd like to try to cut back your drugs.'"
Although it's not known exactly how the 33 genes identified by the researchers affect the development of tolerance, the expression and function of nearly one-third are controlled by a regulatory molecule called TGFbeta. Sarwal and her colleague speculate that the genes somehow affect the development of immune cells responsible for distinguishing self from non-self. But they caution that even long-term tolerance may not last forever; immune challenges such as severe infection can sometimes cause rejection of a donated organ years after anti-rejection medication was successfully stopped.
"The real value of this technology is the ability to easily and repeatedly monitor patients over long periods of time," said Sarwal. "We can keep an eye on this genetic signature and watch for changes that might indicate the beginning of rejection before any clinical signs are apparent. This could be a very exciting advance for both patients and physicians as it can lead to the ability to, for the first time, safely customize immunosuppression for an individual patient."
Sarwal's Stanford and Packard colleagues include biostatistician Li Li, MD; research scientist Szu-chuan Hsieh, MS; postdoctoral scholar Meixia Zhang, PhD, and Oscar Salvatierra, MD, PhD, professor of surgery and of pediatrics, emeritus. Other co-authors are at the Institut National de la Santé et de la Recherche Médicale in France, China Medical University and other institutions.
The study was funded by grants from the National Institutes of Health, the Clinical Center for Immunological Studies at Stanford University, the Lucile Packard Foundation, the Foundation Progreffe, the Establishment Francais des Greffes, the Roche Organ Transplantation Research Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes Research Foundation.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
Ranked as one of the best pediatric hospitals in the nation by U.S. News & World Report and Child magazine, Lucile Packard Children's Hospital at Stanford is a 264-bed hospital devoted to the care of children and expectant mothers. Providing pediatric and obstetric medical and surgical services and associated with the Stanford University School of Medicine, Packard Children's offers patients locally, regionally and nationally the full range of health care programs and services - from preventive and routine care to the diagnosis and treatment of serious illness and injury. For more information, visit http://www.lpch.org.
The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig
Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
20.11.2017 | Earth Sciences
20.11.2017 | Earth Sciences
20.11.2017 | Life Sciences