Journal
KIDNEY INTERNATIONAL
Volume 87, Issue 5, Pages 984-995Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2014.395
Keywords
biomarker; gene signature; meta-analysis; renal allograft; tolerance; transplantation
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Funding
- INSERM institute
- IHU-CESTI institute
- CENTAURE foundation
- Transplantex Labex
- ABM agency
- ROTRF foundation
- Medical Research Council [MC_PC_15108, MR/L008890/1, G0801537, MR/J006742/1] Funding Source: researchfish
- MRC [G0801537, MR/L008890/1] Funding Source: UKRI
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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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