State of the art on the research for biomarkers allowing individual, tailor-made minimization of immunosuppression.

PURPOSE OF REVIEW

In order to avoid toxic side effects by long-term immunosuppressive treatment, transplant research therefore focuses on new strategies to either induce tolerance or allow partial or complete immunosuppressive weaning whenever possible. This can be only safely achieved when guided by biomarkers reflecting the individual immune reactivity. Here we summarize the recent efforts to identify biomarkers and functional assays which allow an individualized minimization or complete weaning of immunosuppression in stable or 'operational' tolerant transplant patients, respectively.

RECENT FINDINGS

Data obtained by two main collaborative networks, 'RISET' and 'Immune Tolerance Network' have provided a better characterization of operational tolerant kidney patients. In both studies an increased numbers of B cells and a B-cell-associated peripheral gene signature were discovered. Long-term observation of tolerant liver transplant patients undergoing immunosuppressive minimization highlight the importance of surveillance or protocol biopsies. Additionally, functional assays such as IFN-γ ELISPOT or urine markers have been shown to predict long-term graft outcome.

SUMMARY

With the recent findings we have gained a better understanding of operational tolerant patients and have identified biomarkers and assays which will be very helpful when guiding partial or complete immunosuppressive minimization. For the future, collaborative efforts are needed to design and perform prospective multicenter trials to validate the identified biomarkers across different laboratories and laboratory platforms.