NIH logoAfter a kidney transplant a patient seemingly undergoes the immuno – suppressive therapy regimens, which probably come along with toxic side effects and elevate risks to infections and cancer. A unique pattern of gene expression in the largest reported group of kidney transplant recipients has been supposedly discovered by the National Institute of Allergy and Infectious Diseases (NIAID). These patients have not rejected the transplanted kidneys even after rejecting immunosuppressive drugs.

There are a large number of patients whoo are subjected to a kidney transplant. In the United States itself more than 80,000 people apparently lived with a kidney transplant in 2008. All the patients ought to go through an immunosuppressive therapy regimen, because the immune systems of the patients possibly refuse to accept the transplanted organ.

Anthony S. Fauci, M.D., NIAID Director remarked, “The immunosuppressive therapy regimens that organ transplant recipients must endure have toxic side effects and increase the recipients’ vulnerability to infections and cancer. This study holds promise for identifying kidney transplant recipients who might be able to minimize or withdraw from their use of anti-rejection drugs. However, large, prospective studies will be necessary to determine if the same biomarkers identified in the current study are reliable predictors of immune tolerance.”

This therapy in return restricts the entire immune system, making the body unable to fight against infections, and various illnesses caused due to a weak immune system, like cancer. Patients may also suffer from diabetes, hypertension and heart disease, as well as swelling, weight gain, and excessive hair growth and acne due to the therapy.

The side effects of this therapy are regarded to be so troublesome, that some patients decide to reduce or completely stop the intake of immunosuppressive drugs on their own accord, therefore risk losing their transplanted organ. Even after the drug is stopped a very small percentage of patients do not face a rejection. Physicians seldom recommend patients to stop the therapy incase the patients reveals signs of cancer or infections that can be fatal.

Dr. Newell shared, “We expected to find a difference between the tolerant and immunosuppression groups in the genes associated with Tregs. However, we were surprised that our data showed that B cell genes may play an important role in maintaining and possibly inducing tolerance to transplanted organs.”

Fewer patients do not face a rejection of the transplanted organ, even after terminating the drugs and the study intended to analyze such patients. The authors examined 25 patients who had undergone a kidney transplant and stopped the immunosuppressive drugs against the advice of their physicians. Even after the stoppage they enjoyed a normal kidney function for more than one year.

Their results were compared to a group of patients who displayed healthy kidneys and at the same time were receiving their immunosuppressive medication. The other group consisted of healthy, non-transplant controlled individuals. Blood samples of all the participants were acquired and observed for their gene expression. The authors then identified a distinct pattern of genes expressed by B cells, a type of white blood cell in the blood of patients who refused the medication.

Dr. Turka quoted, “If we could develop a reliable tolerance signature—a pattern of gene expression that indicates that someone will not reject a transplant—then we could find patients who would make good candidates for supervised drug withdrawal”

The similar pattern was not discovered in the blood of the patients belonging to either of the two groups. They also analyzed a pattern of expression of three B cell genes in the patients who had avoided the drugs. It has been apparently identified that the white blood cells are comprised of T and B cells. While the T cells are called regulatory T cells (Tregs), the B cells appear to promote immune tolerance.

Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID said, “The goal of ITN is to understand how immune tolerance can be induced or achieved in a variety of settings, including allergy, autoimmune disease and transplantation. Potentially, a biomarker for tolerance in kidney transplant recipients may predict tolerance in individuals following transplantation of other organs or with other immune-mediated diseases. Having a cooperative program like ITN allows investigators to explore this possibility and apply the findings of one study across different fields of clinical research.”

The authors aim to determine the potential biomarkers of immune tolerance as it seemingly aids in deciding the patients who can undergo a reduced immunosuppression therapy. They further advice that patients should not deprive themselves of the medication, as it may lead to rejection of the transplanted kidney, or the need for another transplant.

The study was published online in the Journal of Clinical Investigation.