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

Authors
  • Sagoo, Pervinder
  • Perucha, Esperanza
  • Sawitzki, Birgit
  • Tomiuk, Stefan
  • Stephens, David A
  • Miqueu, Patrick
  • Chapman, Stephanie
  • Craciun, Ligia
  • Sergeant, Ruhena
  • Brouard, Sophie
  • Rovis, Flavia
  • Jimenez, Elvira
  • Ballow, Amany
  • Giral, Magali
  • Rebollo-Mesa, Irene
  • Le Moine, Alain
  • Braudeau, Cecile
  • Hilton, Rachel
  • Gerstmayer, Bernhard
  • Bourcier, Katarzyna
  • And 14 more
Type
Published Article
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Publication Date
Jun 01, 2010
Volume
120
Issue
6
Pages
1848–1861
Identifiers
DOI: 10.1172/JCI39922
PMID: 20501943
Source
Medline
License
Unknown

Abstract

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.

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