c l i n i c a l
f o l i o s :
d i s c u s s i o n
Transplant Immunology
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Transplant Immunology | ||
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Related narratives: Kidney Transplant, Heart Transplant, Donor Heart Procurement Transplantation is the most effective means by which organ function is restored in certain disease states. However curtailing the body's immune response to transplanted tissue with the use of powerful immunosuppressant medications remains a major drawback. Steroids have been an effective cornerstone for this therapy since the 1960's, but are also associated with dire side effects. Other pharmacological agents with differing mechanisms of action (calcineurin inhibition, antiproliferative, etc) are used in combination therapy in an attempt to reduce overall steroid dosing. Transplant physicians are now exploring ways to further reduce or even eliminate the need for long term steroid dependence in transplantation. These efforts have focused on the use of induction agents which either deplete lymphocytes or inhibit the IL-2 receptor and are given at the time of transplantation. Maintenance (long term) immunosupression is then achieved with the combination of either calcineurin inhibition (tacrolimus), antiproliferative agents (mycophenolate) or TOR inhibitors (sirolimus) with steroids reserved for rejection episodes and specific patient populations. This approach of steroid minimization has been achieved without increasing graft loss, and has been applicable to different organs in varied patient subgroups such as African Americans and children. With the adoption of induction protocols utilizing lymphocyte depletion or IL-2 inhibition, and the use of newer maintenance agents such as mycophenolate, tacrolimus and sirolimus, detrimental steroid side effects have been reduced without compromising organ longevity. Transplant clinicians now have the ability to reserve steroids solely for first line treatment of rejection. While this approach has reduced the overall burden of steroids and immunosupression, the chronic loss of grafts remains a significant problem. Current research efforts are focusing on refining the balance between chronic allograft loss and the side effects from immunosuppressive therapy, with the ultimate goal of transplant tolerance yet to be realized. Eric Elster, MD, FACS References: Eric Elster, Douglas A. Hale, Roslyn B. Mannon, Linda C. Cendales, S. John Swanson, and Allan D. Kirk. The Road to Tolerance: Renal Transplant Tolerance Induction in Non-Human Primate Studies and Clinical Trials. Transplant Immunology. 2004 Sep-Oct; 13(2):87-99. Gaoxing Lou, Edward M. Falta and Eric A. Elster. Steroid-Free Immunosupression In Organ Transplantation. Current Diabetes Reports. 2005 Aug;5(4):305-10.
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