Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

Abstract

After pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacterial infections and is associated with serious side effects. It is therefore crucial to achieve the optimal individual balance between over- and under-immunosuppression and thereby avoid unnecessary exposure to immunosuppressive drugs. In routine use, steering of immunosuppressants is performed primarily by monitoring of trough levels that mirror pharmacokinetics (although not, however, pharmacodynamics). Other diagnostic and prognostic markers to assess the individual intensity of immunosuppression are missing. Potential methods to determine immune function and grade of immunosuppression, such as analysis of the torque teno virus (TTV) load, QuantiFERON Monitor®, and ImmuKnow® as well as virus-specific T cells (Tvis), are currently being evaluated. In some studies TTV load, QuantiFERON Monitor® and ImmuKnow® were associated with the risk for post-transplant rejections and infections, but randomized controlled trials after pediatric kidney transplantation are not available. Post-transplant monitoring of Tvis levels seem to be promising because Tvis control virus replication and have been shown to correlate with virus-specific as well as general cellular immune defense, which represents the individual’s susceptibility to infections. Additional Tvis-monitoring provides an innovative opportunity to personalize the antiviral management and the dosing of the immunosuppressive therapy after pediatric kidney transplantation to avoid unnecessary therapeutic interventions and identify over-immunosuppression.

The predictive value of peripheral blood CD4 cells ATP concentration for immune-related adverse events in advanced non-small cell lung cancer patients

“…The selection of these predictive indicators and the establishment of cutoff values are valuable for understanding the risk factors associated with irAEs. These findings can assist clinicians in optimizing treatment strategies and implementing appropriate monitoring and management protocols for patients undergoing immunotherapy [ 30 , 31 ]. By adopting a more individualized approach to therapy, balancing the potential benefits of ICIs with the risks of developing irAEs becomes possible.…”

The predictive value of peripheral blood CD4 cells ATP concentration for immune-related adverse events in advanced non-small cell lung cancer patients

“…The selection of these predictive indicators and the establishment of cutoff values are valuable for understanding the risk factors associated with irAEs. These ndings can assist clinicians in optimizing treatment strategies and implementing appropriate monitoring and management protocols for patients undergoing immunotherapy [25,26]. By adopting a more individualized approach to therapy, balancing the potential bene ts of ICIs with the risks of developing irAEs becomes possible It is important to acknowledge the limitations of this study.…”

Torque‐teno virus for the prediction of graft rejection and infection disease after kidney transplantation: A systematic review and meta‐analysis

“…26,27 Due to the natural non-pathogenicity and immune function monitoring properties of TTV, there has been an increasing interest in the potential use of TTV DNA load as a novel functional marker of immune status. 5,[28][29][30][31] TTV DNA load increased rapidly from Days 7 to 30, peaked 3−12 months after KT, and then decreased gradually. 18,19,[32][33][34] Previous studies suggested a potential of TTV quantification for risk prediction of infectious diseases and rejection events in KT recipients.…”

“…Of note, the virus is unaffected by conventional antiviral drugs 17,25 and inversely correlated with the number and function of T‐lymphocytes 26,27 . Due to the natural non‐pathogenicity and immune function monitoring properties of TTV, there has been an increasing interest in the potential use of TTV DNA load as a novel functional marker of immune status 5,28–31 …”