Biomarkers and immunopathology of tolerance.

PURPOSE OF REVIEW: This article describes biomarkers capable of identifying and predicting operational tolerance in solid organ transplant recipients. We outline the utility of these biomarkers in distinguishing allograft recipients in whom toxic immunosuppressive therapies might safely be minimized or withdrawn, and discuss their value in the appraisal of tolerance induction strategies. Finally, we review the insights derived from biomarker discovery into the cellular mechanisms underlying allograft tolerance.

RECENT FINDINGS: Important progress has been made in the development of robust signatures of tolerance, in both renal and liver transplant settings. Methodological advances, including high-throughput sequencing and bioinformatic processes, have been brought to bear on biomarker discovery and have heralded improvements in the accuracy with which operational tolerance can be predicted. Although the immunopathological basis for donor-specific tolerance is increasingly recognized to involve a complex interplay between numerous cell types, we review new lines of evidence shedding light on these mechanisms.

SUMMARY: Significant recent progress in identifying robust tolerance biomarkers has been made. In recognition of the need for rigorous validation of these, the first biomarker-led prospective immunosuppression withdrawal trials are underway. Such projects promise further progress and refinement in tolerance biomarker discovery, and offer hope for the amelioration of the burden associated with immunosuppressive therapies.