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Estudio provee esperanza para que los pacientes transplantados vivan sin medicamentos contra el rechazo, dicen investigadores de

Study provides hope that some transplant patients could live free of anti-rejection drugs, Packard/Stanford researchers say

By Krista Conger

STANFORD, Calif. — 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, 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

Courtesy of Stanford School of Medicine

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