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
