Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans

Pervinder Sagoo, Esperanza Perucha, Birgit Sawitzki, Stefan Tomiuk, David A. Stephens, Patrick Miqueu, Stephanie Chapman, Ligia Craciun, Ruhena Sergeant, Sophie Brouard, Flavia Rovis, Elvira Jimenez, Amany Ballow, Magali Giral, Irene Rebollo-Mesa, Alain Le Moine, Cecile Braudeau, Rachel Hilton, Bernhard Gerstmayer, Katarzyna BourcierAdnan Sharif, Magdalena Krajewska, Graham M. Lord, Ian Roberts, Michel Goldman, Kathryn J. Wood, Kenneth Newell, Vicki Seyfert-Margolis, Anthony N. Warrens, Uwe Janssen, Hans-Dieter Volk, Jean-Paul Soulillou, Maria P. Hernandez-Fuentes, Robert I. Lechler

Research output: Contribution to journalArticlepeer-review

455 Citations (Scopus)


Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to alpha-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell-related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients.
Original languageEnglish
Pages (from-to)1848 - 1861
Number of pages14
JournalJournal of Clinical Investigation
Issue number6
Publication statusPublished - 1 Jun 2010


  • Biological Markers
  • Humans
  • Immune Tolerance
  • Immunosuppressive Agents
  • Kidney Transplantation
  • T-Lymphocytes
  • Tissue Donors


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