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.
