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Gene Pattern Marks Transplant Patients Who Can Avoid Lifelong Drugs

Scientists have identified a distinctive genetic signature in patients who successfully stopped taking a lifelong regimen of immunosuppressive drugs after having a kidney transplant. The finding may help to identify other transplant recipients who could safely reduce or end their use of harsh drugs that block transplant rejection.

The kidney is the most common transplanted organ nationwide, with more than 16,000 kidney transplantations performed last year. To keep the immune system from attacking transplanted organs, patients must take immunosuppressive drugs for the rest of their lives. But these drugs suppress the entire immune system, which can make it hard to fight off infections. The drugs may also boost the risk for cancer and other conditions.

Kidney transplants nearly always fail if patients stop taking their immunosuppressive drugs. But for a tiny percentage of these cases, the transplants aren't rejected. Two independent research teams—one based in the United States and the other in Europe—decided to take a closer look at these unusual patients. The studies were supported by the Immune Tolerance Network, an international research consortium funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), along with the Juvenile Diabetes Research Foundation International.

The researchers identified and studied rare transplant recipients who had stable, well-functioning kidney transplants despite being off their immunosuppressive medications for more than a year. These patients (25 in the U.S. and 11 in Europe) had developed tolerance for the transplants. They were compared to kidney transplant recipients still taking immunosuppressive drugs and to healthy controls. The studies were published in separate papers in the June 2010 issue of the Journal of Clinical Investigation.

The U.S. team analyzed gene expression in participants’ blood cells. They found that the tolerant transplant recipients had a unique pattern of genes expressed in B cells, a type of white blood cell. Further study identified an expression pattern of 3 genes in B cells that was far more common in tolerant transplant recipients than in those taking immunosuppressive drugs.

Similar findings were observed by the European group. When their initial analyses were completed, the 2 research teams shared their samples. Cross-validation studies confirmed that the B cell gene patterns and markers were strongly linked to transplant tolerance. The findings suggest that a B cell gene signature may ultimately help to identify transplant recipients who may be good candidates to be weaned off of immunosuppressive drugs.

"This study holds promise for identifying kidney transplant recipients who might be able to minimize or withdraw from their use of anti-rejection drugs," says NIAID Director Dr. Anthony S. Fauci. "However, large, prospective studies will be necessary to determine if the same biomarkers identified in the current study are reliable predictors of immune tolerance."

The researchers stress that transplant patients should never consider reducing or changing their medication regimen unless under the direct supervision of their physician.