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A Common Gene Signature Across Multiple Studies Identifies Biomarkers and Functional Regulation in Tolerance to Renal Allograft

D. Baron,1,2,3 G. Ramstein,4 M. Chesneau,1,2,3 Y. Echasseriau,1,2,3 A. Pallier,1,2,3 C. Paul,1,2,3 N. Degauque,1,2,3 M. Hernandez-Fuentes,5 A. Sanchez-Fueyo,6 K. Newell,7 M. Giral,1,2,3 J.-P. Soulillou,1,2,3 R. Houlgatte,8,9 S. Brouard.1,2,3

1UMR 1064 - CRTI, INSERM, Nantes, Loire Atlantique (44), France
2ITUN, CHU de Nantes, Nantes, Loire Atlantique (44), France
3Faculté
de Médecine, Université
de Nantes, Nantes, Loire Atlantique (44), France
4UMR 6241 - LINA, Université
de Nantes, Nantes, Loire Atlantique (44), France
5MRC Centre for Transplantation, King's College London, London, United Kingdom
6Institute of Liver Studies, King's College Hospital, London, United Kingdom
7Department of Surgery, Emory University, Atlanta, GA
8U954 - LNGERE, INSERM, Nancy, France
9DRCI, CHU de Nancy, Nancy, France.

Meeting: 2015 American Transplant Congress

Abstract number: 234

Keywords: Gene expression, Genomic markers, Kidney transplantation, Tolerance

Session Information

Date: Monday, May 4, 2015

Session Name: Concurrent Session: Tolerance: Clinical Studies

Session Time: 2:15pm-3:45pm

 Presentation Time: 2:15pm-2:27pm

Location: Room 122-AB

Related Abstracts
  • Three-Gene Signature of Tolerance for Clinical Application in Kidney Transplant Recipients
  • Non-Chimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers

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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To cite this abstract in AMA style:

Baron D, Ramstein G, Chesneau M, Echasseriau Y, Pallier A, Paul C, Degauque N, Hernandez-Fuentes M, Sanchez-Fueyo A, Newell K, Giral M, Soulillou J-P, Houlgatte R, Brouard S. A Common Gene Signature Across Multiple Studies Identifies Biomarkers and Functional Regulation in Tolerance to Renal Allograft [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/a-common-gene-signature-across-multiple-studies-identifies-biomarkers-and-functional-regulation-in-tolerance-to-renal-allograft/. Accessed January 19, 2021.

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