Immunosuppression Monitoring-What Clinician Needs to Know?

Abstract

The liver is well known for its immunotolerance, but rejection without immunosuppression is frequently encountered post liver transplantation, especially in humans.¹ Indeed, the amount of immunosuppression required post liver transplant is less compared to other organ transplants like kidney, heart, and intestine.² Reports of successful weaning of immunosuppression have been reported but are not practiced for fear of unwanted alloimmune response leading to rejection. Life-long immunosuppression is needed in most patients for graft survival but is associated with side effects like renal dysfunction, metabolic abnormalities, or risk of de novo malignancies. Also, the appropriate dose of immunosuppression to achieve adequate graft function and prevention of toxicities is very important. One shoe does not fit all. There are significant individual variations in response and side effect profile. Also, the level of immunosuppression varies with the underlying liver disease like autoimmune disease requires higher immunosuppression. Thus, monitoring the adequate immunosuppression with the minimization of drug toxicity is imperative post-transplant. Unfortunately, the current methods for immunosuppression monitoring rely on testing the immunosuppressive drug levels rather than the immune system activity. We have discussed the concept of alloreactivity, available methods of immunosuppression and drug monitoring and investigational methods in this review.

Keywords: immunosuppression; monitoring; t cell activation assays; tacrolimus.

Figure 1

Targets for current immunosuppressive drugs. Abbreviations: TCR, T-cell receptor; MHC, major histocompatibility complex; APC, antigen presenting cells; NFAT, nuclear factor of T-cell activation; mTOR, mammalian (mechanistic) target of rapamycin; MMF, mycophenolate mophetil.