Patients tolerant to a kidney graft display a specific blood transcriptional pattern but reported results from five distinct studies hardly overlapped, raising the question of pertinence for future clinical application. The objective of this collaborative work was to identify a common gene signature, specific functional and cellular components, and discriminating biomarkers.

Our work was based on bioinformatic methods for integration and interpretation of genomic data. Class predictions of samples were performed using a discriminative Support Vector Machine classifier. Experimental validation was performed on new samples using real-time quantitative RT-PCR.

A meta-analysis of these studies, gathering 96 tolerant samples, identified a robust gene signature involving proliferation of B and CD4 T-cells, and inhibition of CD14 monocyte related functions. This signature could be further validated through a cross-validation approach, yielding 92.5% accuracy independently of the study of origin. Besides, an 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 pointed on the participation of other cell subsets in tolerance. The use of the top-20 biomarkers, mostly centred 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. Finally, these data point on a global preservation of genes favouring 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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