Introduction

Immunosuppressive drug therapy is used to prevent acute or chronic rejection of organ allografts in patients who have received a transplant. As with most prophylactic treatments, it only becomes apparent that the treatment has failed when the unwanted event happens. If there is a large safety margin between the dose of drug that prevents the unwanted event and the dose at which unacceptable drug toxicity occurs then the drug dose given can be sufficiently high to ensure treatment effectiveness. However, in transplant patients, the consequences of under- or over-immunosuppression can be equally catastrophic. On the one hand, underimmunosuppression can result in organ rejection that may, in turn, lead to graft loss and even death, while, on the other hand, overimmunosuppression can result in life-threatening infections, carcinoma and a range of drug-related adverse events such as nephrotoxicity. At present, we use plasma or blood drug concentrations as a surrogate measure of immunosuppression in the belief that there is a tight relationship between drug concentration and effect [1]. However, interindividual variation in pharmacological response can make drug concentration data difficult to interpret. For this reason, the use of biomarkers for monitoring the response to immunosuppressive drug therapy has been investigated.

Choice of biomarker

The choice of biomarkers for monitoring the response to immunosuppressive drug therapy is wide. Monitoring the effect of therapy on the primary intracellular drug targets offers the most promise, but these targets are also the most difficult to measure (Table 45.1).