Immune suppressants are a necessary evil for organ transplant recipients. These life-saving drugs must be taken to prevent graft failure, but they come with a long list of potential side effects. Immune suppressed individuals have an increased risk of infection, cancer, diabetes, kidney disease and other complications compared to the general population. There is a huge potential benefit to develop methods to decrease the need for immune suppression in organ transplant recipients.
Some liver transplant recipients have had immune suppression medication stopped due to infections or other complications and have done well off medication. This observation caught the attention of transplant physicians around the world and stimulated clinical research into withdrawal of immune suppression and development of graft tolerance (immune acceptance of an organ graft).
The liver is the only internal human organ capable of regeneration, which puts liver transplant patients at an advantage over those who’ve received a heart, kidney or lung. When liver injury occurs, remaining liver cells can divide and return to normal function. This makes the liver more resistant to attack from the immune system, and makes the patient less dependent on immune-suppression than other transplant recipients.
Although most liver recipients will experience rejection if immune suppression is reduced or stopped, clinicians worldwide have reported cases of adult and pediatric liver transplant recipients who were taken off their immunosuppressant for various reasons with no negative effects. These cases made researchers want to know more about immunosuppressant withdrawal and what was different about these patients’ immune systems that made withdrawal possible.
Research has shown that about 20 percent of adults who’ve undergone liver transplant can maintain normal liver function without immune suppression. Research is ongoing to determine the immunologic profile of these people. What is it about the way their immune system works that makes them tolerant to immunosuppression withdrawal?
A study out of Barcelona is making progress with immunologic “fingerprinting” of this subset of patients, using specific bio-markers to successfully predict which adult liver transplant recipients would be good candidates for drug-weaning protocols.
Sandy Feng, MD of the University of California, San Francisco has completed a phase I clinical trial looking at withdrawal of immune suppression from live donor liver transplant recipients. In the pipeline is a larger, NIH-funded, 10-center study in which CHOP will be involved. The aim will be to determine if immunosuppression can be safely withdrawn from children with liver transplants — both live and deceased donors — and to identify the immunologic profiles children in all categories.
The hope is that by identifying the common characteristics of the immune systems of those who are tolerant to withdrawal of immune suppression, physicians can minimize use of these medications. In the future, this research could support the development of new therapies that modify the function of the immune system to induce tolerance to withdrawal from immunosuppression.
Watch this space for updates on CHOP’s involvement in this exciting research.