Following organ transplantation, the recipient’s immune system identifies the graft as non-self by virtue of differences in donor cell surface markers, such as MHC molecules. An immune response against the graft follows, which will result in the loss of the transplanted organ, unless immunosuppressive agents are used to dampen the immune response.
During the early post-transplant period, patients are at high risk of rejection. Therefore, an intense induction regimen of immunosuppressive agents is used, which usually involves the administration of intravenous or subcutaneous agents, often a combination of intravenous corticosteroids together with a biological agent (see Chapter 15). Some centres (particularly in North America) use lymphocyte depleting antibodies such as anti-thymocyte globulin (ATG) or the monoclonal antibody alemtuzumab (CamPath 1H). In the UK, many centres use an anti-CD25 monoclonal antibody (basiliximab). Following induction therapy, the patient will require long-term maintenance immunosuppression. In contrast to induction agents, these are administered orally, and often consist of triple therapy (for example, a combination of prednisolone (tapering dose), a calcineurin inhibitor such as ciclosporin or tacrolimus, and an anti-proliferative agent such as azathioprine or mycophenolate). If acute rejection does occur, a further intensification of immunosuppression is required, involving the administration of intravenous corticosteroids. The exact immunosuppresive regimen used usually depends on the patient, and balancing their risk of developing rejection with their likely susceptibility to side-effects.