Cytokine-based immune monitoring

Several studies conducted during the last decade have shown that some promising biomarkers and surrogate markers may be useful in implementing personalized immunomodulatory therapies and improving graft and recipient care in solid organ transplantation. The complexity of the immune system response against the implanted graft can change remarkably in the long-term follow-up, and the dynamic balance between T-effector/T-regulatory cell populations determines the outcome of the anti-donor response, risk of rejection, and immunosuppression requirements. For this reason, at any time before and after transplantation, monitoring the T-effector cell activity, associated with an increase in pro-inflammatory cytokine production and release, can be considered as a surrogate marker of the risk of rejection and immunosuppression requirements. Furthermore, infections remain a cause of major complications following transplantation, highlighting the need for developing new approaches aimed at identifying the risk of infection in solid organ recipients. Another main aspect to be considered is that immunosuppressive agents may immunomodulate each treated patient differently. Immunosuppressive drugs show high pharmacokinetic and pharmacodynamic inter-patient variability. Some pharmacodynamic biomarkers such as measurement of the inhibition of target activity can reflect the individual's susceptibility to the treatment. Monitoring a panel of valid biomarkers may provide patient stratification and better immunosuppression treatment selection. After transplantation, therapy should be adjusted based on the prediction of rejection episodes (maintained alloreactivity), prognosis of allograft damage progression, and personal drug response. This review focuses on current knowledge, indicating that monitoring T-cell changes in the production of cytokines such as interferon gamma (IFN-γ) and interleukin (IL)-2, and also the expression of IL-17 by central and effector memory T cells, could be used to predict the risk of rejection and infection, thereby guiding immunosuppressive therapy in transplant recipients.