The pits and pearls in translating operational tolerance biomarkers into clinical practice

This review highlights the importance and the role of key biomarker studies in liver and kidney transplant tolerance, discusses the most recent findings with respect to organ-type and cell-type specificity in blood and tissue, and points out the novel research directions in the field of immunological tolerance that involve both adult and pediatric recipients.

Recent studies indicate that biomarkers for solid organ transplant tolerance are distinct with respect to organ type and cell type, suggesting distinct tolerogenic mechanisms for different organs. In both liver and kidney transplant tolerant recipients, novel cellular mechanisms have been proposed for natural killer cells, B cells, and dendritic cells in the maintenance of stable operational tolerance.

Major advances have been made with respect to the understanding of mechanisms and the process of discovery and early validation of peripheral blood biomarkers for operational transplant tolerance both in kidney and liver transplantation. These studies have shed light on the findings that these tolerance mechanisms may be organ specific, as the peripheral blood transcriptional profiling attempts by microarrays and PCR reveal distinct differences and suggest roles for specific cell types. Although these studies are mostly in adults and limited in children, the first tolerance gene signature for pediatric liver transplant tolerance suggests that there are common mechanisms, yet distinct peripheral biomarkers across age. Prospective trials and organ integrative studies are now needed to further develop these biomarkers for future clinical application in addition to expanding novel approaches such as the investigation of miRNAs to better understand the tolerance mechanisms.