Biomarkers of Operational Tolerance in Clinical Liver Transplantation

Alberto Sanchez-Fueyo, University of Barcelona, Barcelona, Spain

A proportion of liver transplant recipients can spontaneously accept their grafts in the absence of immunosuppression (operational tolerance). Unfortunately, we lack accurate predictive markers to identify tolerant liver recipients before therapy is discontinued. Our work has been focused on the search of transcriptional and cell phenotypic biomarkers of tolerance in liver transplantation. Tolerant and non-tolerant liver recipients differ in their blood gene expression profiles. These differences are associated with an expansion of NK cells in the blood of tolerant recipients, and are already detectable before immunosuppressive drugs are discontinued. On the other hand, analysis of liver tissue samples obtained before drug withdrawal reveals that tolerant and non-tolerant grafts differ in an unexpectedly small number of genes, many of which are involved in the regulation of iron metabolism. These findings will likely provide useful diagnostic markers to screen patients for immunosuppression minimization strategies.