The researchers used 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.
They 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 ten 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.
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. The researchers 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.
MEDICA.de; Source: Stanford University Medical Center