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A common gene signature across multiple studies relate biomarkers and functional regulation in tolerance to renal allograft

Research output: Contribution to journalArticlepeer-review

Daniel Baron, Gérard Ramstein, Mélanie Chesneau, Yann Echasseriau, Annaick Pallier, Chloé Paul, Nicolas Degauque, Maria P Hernandez-Fuentes, Alberto Sanchez-Fueyo, Kenneth A Newell, Magali Giral, Jean-Paul Soulillou, Rémi Houlgatte, Sophie Brouard

Original languageEnglish
Pages (from-to)984-995
Number of pages12
JournalKidney International
Volume87
Issue number5
DOIs
E-pub ahead of print28 Jan 2015

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  • ki2014395a

    ki2014395a.pdf, 4.89 MB, application/pdf

    Uploaded date:04 Jan 2016

    Licence:CC BY-NC-ND

King's Authors

Abstract

Patients tolerant to a kidney graft display a specific blood cell transcriptional pattern but results from five different studies were inconsistent, raising the question of relevance for future clinical application. To resolve this, we sought to identify a common gene signature, specific functional and cellular components, and discriminating biomarkers for tolerance following kidney transplantation. A meta-analysis of studies identified a robust gene signature involving proliferation of B and CD4 T cells, and inhibition of CD14 monocyte related functions among 96 tolerant samples. This signature was further supported through a cross-validation approach, yielding 92.5% accuracy independent of the study of origin. Experimental validation, performed on new tolerant samples and using a selection of the top-20 biomarkers, returned 91.7% of good classification. Beyond the confirmation of B-cell involvement, our data also indicated participation of other cell subsets in tolerance. Thus, the use of the top 20 biomarkers, mostly centered on B cells, may provide a common and standardized tool towards personalized medicine for the monitoring of tolerant or low-risk patients among kidney allotransplant recipients. These data point to a global preservation of genes favoring the maintenance of a homeostatic and 'healthy' environment in tolerant patients and may contribute to a better understanding of tolerance maintenance mechanisms.

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