Gene Pattern Identified in Kidney Transplant Recipients who have Successfully Stopped Taking Anti-Rejection Drugs

June 2010

Since September 2003, Dr. Kenneth Newell has been Emory's principal investigator of an Immune Tolerance Network (ITN), multi-center study of a handful of kidney transplant recipients who were able to stop taking immunosuppressive drugs without serious effects. In the June 2010 edition of the Journal of Clinical Investigation, Dr. Newell is the lead author of a paper reporting the study's findings, particularly the researchers' identification of a pattern of genes turned on in these rare individuals' white blood cells which may eventually be used to help identify other transplant recipients who could reduce or completely taper their immunosuppressive therapy.

Dr. Newell and his co-authors emphasize that their study examined "tolerant" patients who had stopped taking their prescribed immunosuppressive medications for at least one year, yet did not reject their kidneys. They are not encouraging other recipients to do the same. "In the vast majority of patients, stopping or reducing immunosuppression medications without doctor supervision will have serious health consequences, including loss of the transplanted kidney," cautions Dr. Newell.

In the study, 25 of these tolerant patients were compared with two other groups: recipients who were still taking their medication and had healthy kidneys, and healthy, non-transplanted controls.

The ITN team analyzed the genes turned on in samples of blood cells from each of the three groups and found that the tolerant recipients had a distinct pattern of genes turned on in B cells, a type of white blood cell. Further study showed that zeroing in on three B cell genes could distinguish patients who had stopped taking their medications yet maintained good graft function. While most studies of immune tolerance have focused on the role of regulatory T cells, a subset of the T white blood cell, more recent work has indicated that some kinds of B cells may also help regulate the immune system and promote tolerance of a transplanted organ.

"The signature that we discovered in these individuals may be useful for identifying kidney transplant recipients who are already tolerant. Whether or not this same signature will identify those kidney transplant recipients still taking immunosuppressive medications who are predisposed to developing tolerance in the future is unknown," Dr. Newell says. "Carefully supervised studies will be necessary to answer this question as well as to determine whether attempting to completely withdraw all immunosuppressive drugs will prove advantageous in the long term."

The paper was entitled "Identification of a B cell signature associated with renal transplant tolerance in humans." The study was supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes, Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation.