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A 'biomarker signature' for tolerance in transplantation

Nature Reviews Nephrology volume 6, pages 606–613 (2010)Cite this article

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Abstract

In the past decade, an explosion in the number of high-throughput tools for the measurement of different cellular products has occurred. These tools have the potential to further our understanding of human disease and this development has facilitated the identification of new biomarkers in all areas of medicine. In the field of solid organ transplantation, two different areas have developed: the use of biomarkers to predict allograft tolerance for the identification of patients who can be weaned from immunosuppressive therapy, and biomarkers for the prediction of allograft rejection, so that parenchymal damage can be prevented before it becomes irreversible. In this Review, we discuss the development of biomarkers that are indicative of transplant tolerance. Identifying patients in whom donor-specific tolerance has developed would constitute a major advance in the care of organ transplant recipients. This ability would allow the minimization or even the withdrawal of immunosuppressive therapy in selected patients, thus reducing the number of adverse effects and costs, and optimizing long-term graft outcomes. The routine clinical use of these biomarkers, once validated, would bring to the fore the possibility of personalized medicine.

Key Points

  • The use of biomarkers may allow the possibility of personalized medicine in fields such as renal transplantation

  • In the follow-up of solid organ transplant recipients, validated biomarkers of tolerance may be as clinically useful as biomarkers of rejection

  • Biomarkers of tolerance may be used in the future to identify patients in whom immunosuppression can be weaned or even withdrawn

  • Such biomarkers could also be used to establish the success of tolerance-inducing protocols

  • Cross-platform biomarkers may be more effective at identifying tolerance than single biomarkers

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Figure 1: Opportunities to modify the management of transplant recipients according to their biomarker signature.

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Acknowledgements

M. P. Hernandez-Fuentes and R. I. Lechler acknowledge financial support from the EU (QLRT–2002–02127, from FP5), Immune Tolerance Network (ITN503ST), RISET consortium (512090 IP, from FP6), MRC (G0801537/ID: 88245) and Guy's & St Thomas' Charity (Grant 080530). M. P. Hernandez-Fuentes acknowledges financial support from the Department of Health via the NIH Research (NIHR) comprehensive Biomedical Research Center award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.

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Authors and Affiliations

  1. Medical Research Council Centre for Transplantation, King's College London, Great Maze Pond, SE1 9RT, London, UK

    Maria P. Hernandez-Fuentes

  2. King's Health Partners, Room 1.4 Hodgkin Building, Guy's Hospital, SE1 1UL, London, UK

    Robert I. Lechler

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M. P. Hernandez-Fuentes and R. I. Lechler substantially contributed to the discussion of content and reviewed/edited the manuscript before submission. M. P. Hernandez-Fuentes also researched data for the article and wrote the article.

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Correspondence to Robert I. Lechler.

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M. P. Hernandez-Fuentes and R. I. Lechler have a patent application with King's College London.

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Hernandez-Fuentes, M., Lechler, R. A 'biomarker signature' for tolerance in transplantation. Nat Rev Nephrol 6, 606–613 (2010). https://doi.org/10.1038/nrneph.2010.112

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