Abstract
Liver transplantation offers a unique window into transplant immunology due, in part, to the considerable proportion of recipients who develop immunological tolerance to their allograft. Biomarkers are able to identify and predict such a state of tolerance, and thereby able to establish suitable candidates for the minimization of hazardous immunosuppressive therapies, are not only of great potential clinical benefit but might also shed light on the immunological mechanisms underlying tolerance and rejection. Here, we review the emergent transcriptomic technologies serving as drivers of biomarker discovery, we appraise efforts to identify a molecular signature of liver allograft tolerance, and we consider the implications of this work on the mechanistic understanding of immunological tolerance.
Highlights
The liver represents a unique window to the immune system
Accurate prognostic model developed using intragraft expression profiles, mainly enriched with genes involved in iron homeostasis
The intragraft expression profile was mainly enriched with genes involved in iron homeostasis, and showed no overlap with genes identified from peripheral blood mononuclear cell (PBMC)
Summary
The liver represents a unique window to the immune system. Unlike other transplanted organs, it exhibits immunoregulatory, tolerogenic properties, enabling an allograft to be more readily spontaneously accepted. The propensity to tolerance was noted to develop over time, with those who had had their graft for 10.6 years or more achieving tolerance in 79.2% of cases [3] While these results should be taken with some caution, the inescapable implication is that a significant proportion of liver transplant recipients, if in the second decade of graft survival, are unnecessarily subjected to immunosuppressive therapy and the significant risks associated with it. The systems biology approach has developed to offer a computational and mathematical framework enabling the integration and analysis of data from these seemingly disparate fields The application of these developing fields to the arena of transplantation, with a view to the personalized treatment of patients, has recently been dubbed as “transplantomics” [4, 5]. We consider the implications of these tools on our mechanistic understanding of operational tolerance and how this might guide future therapeutic developments
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