title: A common gene signature across multiple studies relate biomarkers and functional regulation in tolerance to renal allograft.
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.
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Daniel
authors: D
authors: Baron
authors: LINA COD, UMR 6241, Université de Nantes, Ecole des Mines de Nantes and CNRS, Nantes, France.
authors: Gérard
authors: G
authors: Ramstein
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Mélanie
authors: M
authors: Chesneau
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Yann
authors: Y
authors: Echasseriau
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Annaick
authors: A
authors: Pallier
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Chloé
authors: C
authors: Paul
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Nicolas
authors: N
authors: Degauque
authors: MRC Centre for Transplantation, King's College London, London, UK.
authors: Maria P
authors: MP
authors: Hernandez-Fuentes
authors: Institute of Liver Studies, King's College Hospital, Denmark Hill, King's College London, London, UK.
authors: Alberto
authors: A
authors: Sanchez-Fueyo
authors: Department of Surgery, Emory University, Atlanta, Georgia, USA.
authors: Kenneth A
authors: KA
authors: Newell
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Magali
authors: M
authors: Giral
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Jean-Paul
authors: JP
authors: Soulillou
authors: 1] Inserm, U954, Nancy, France [2] CHU de Nancy, DRCI, Nancy, France.
authors: Rémi
authors: R
authors: Houlgatte
authors: 1] INSERM, UMR 1064, Nantes, France [2] CHU de Nantes, ITUN, Nantes, France [3] Université de Nantes, Faculté de Médecine, Nantes, France.
authors: Sophie
authors: S
authors: Brouard
mesh_terms: D064591:Allografts / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000502:physiology; D059467:Transcriptome
chemical_list: D015415:Biomarkers
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