A common gene signature across multiple studies relate biomarkers and functional regulation in tolerance to renal allograft.
Fiche publication
Date publication
mai 2015
Journal
Kidney international
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HOULGATTE Rémy
Tous les auteurs :
Baron D, Ramstein G, Chesneau M, Echasseriau Y, Pallier A, Paul C, Degauque N, Hernandez-Fuentes MP, Sanchez-Fueyo A, Newell KA, Giral M, Soulillou JP, Houlgatte R, Brouard S
Lien Pubmed
Résumé
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.
Mots clés
Allografts, immunology, Biomarkers, blood, Humans, Immune Tolerance, genetics, Kidney Transplantation, Leukocytes, Mononuclear, physiology, Transcriptome
Référence
Kidney Int.. 2015 May;87(5):984-95