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
|Contact: Krista Conger|
Stanford University Medical Center