Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study provides hope that some transplant patients could live free of anti-rejection drugs

22.08.2007
People with organ transplants, resigned to a lifetime of anti-rejection drugs, may now have reason to hope for a respite, say researchers at Lucile Packard Children's Hospital and the Stanford University School of Medicine. Using a simple blood sample, the scientists have identified for the first time a pattern of gene expression shared by a small group of patients who beat the odds and remained healthy for years without medication.

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.

Krista Conger | EurekAlert!
Further information:
http://mednews.stanford.edu
http://www.lpch.org

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>