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.
Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung
High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences