Prevention of Transplant Rejection

Abstract

In the past 2 decades, progressive improvements in the results of organ transplantation as a therapeutic strategy for patients with end-stage organ disease have been achieved due to greater insight into the immunobiology of graft rejection and better measures for surgical and medical management. It is now known that T cells play a central role in the specific immune response of acute allograft rejection. Strategies to prevent T cell activation or effector function are thus all potentially useful for immunosuppression. Standard immunosuppressive therapy in renal transplantation consists of baseline therapy to prevent rejection and short courses of high-dose corticosteroids or monoclonal or polyclonal antibodies as treatment of ongoing rejection episodes. Triple-drug therapy with the combination of cyclosporin, corticosteroids and azathioprine is now the most frequently used immunosuppressive drug regimen in cadaveric kidney recipients. The continuing search for more selective and specific agents has become, in the past decade, one of the priorities for transplant medicine. Some of these compounds are now entering routine clinical practice: among them are tacrolimus (which has a mechanism of action similar to that of cyclosporin), mycophenolate mofetil and mizoribine (which selectively inhibit the enzyme inosine monophosphate dehydrogenase, the rate-limiting enzyme for de novo purine synthesis during cell division), and sirolimus (rapamycin) [which acts on and inhibits kinase homologues required for cell-cycle progression in response to growth factors, like interleukin-2 (IL-2)]. Other new pharmacological strategies and innovative approaches to organ transplantation are also under development. Application of this technology will offer enormous potential not only for the investigation of mechanisms and mediators of graft rejection but also for therapeutic intervention.

Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems

“…Although these infections are readily controlled by healthy individuals, they may become systemic in immunocompromised individuals, hospitalized patients, or individuals with inherited mutations in immune genes. Calcineurin is a phosphatase involved in the activation of NFAT transcription factors, and calcineurin inhibitors, such as cyclosporine A (CsA) and tacrolimus, are commonly used as immunosuppressors for treating acute transplant rejection (10), autoimmune diseases (such as psoriasis) (11), and other immunological conditions (such as atopic dermatitis) (12). Although such inhibitors are highly efficient, they have potent side effects that include susceptibility to opportunistic infections from pathogens, such as Candida albicans , Aspergillus fumigatus , and many bacterial species, which are normally well controlled by innate and adaptive immunity (13, 14).…”

Allergic sensitization in kidney-transplanted patients prevails under tacrolimus treatment

“…Lifelong immunosuppressive therapy is a prerequisite for successful organ transplantation. The immunosuppressive drugs applied target mainly the specific immune response, in particular T lymphocytes [1]; consequently, some of the same drugs applied in transplantation medicine are used in severe allergic diseases as well [2, 3]. Therefore, one would expect that transplant recipients do not show clinical signs of type I allergy.…”

Nonviral and Viral Gene Transfer to the Kidney in the Context of Transplantation

“…Acute rejection of vascularized grafts can be prevented by immunosuppressive medications currently available, but few of the new ones look especially promising [1]. These compounds inhibit the immune response rather unselectively and therefore raise the risk of infections and cancer [1]quite substantially.…”

“…These compounds inhibit the immune response rather unselectively and therefore raise the risk of infections and cancer [1]quite substantially. Recent exciting developments of in vivo gene transfer techniques would ideally target the isolated organ before transplantation, providing a real alternative to systemic immunosuppression.…”