Transcriptomics

Dataset Information

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Indices of Tolerance (IOT): Cross-platform biomarkers that identify kidney transplant tolerance


ABSTRACT: Being able to identify patients in whom immunological tolerance has been established or is developing would allow an individually tailored approach to post-transplant management of kidney allograft recipients. Ex vivo immunological monitoring was performed on samples from five groups of European renal transplant recipients (“IOT samples”): ten drug-free tolerant recipients who were functionally stable despite remaining immunosuppression-free for more than one year (Tol-DF); also functionally stable patients on minimal immunosuppression (<10 mg/day prednisone, s-LP); stable patients maintained with calcineurin inhibitors (s-CNI); stable patients maintained on CNI-free immunosuppression regimen (s-nCNI); patients showing signs of chronic rejection (CR) and healthy controls (HC). Among the investigation of other biomarkers and bioassays, gene expression profiles were generated on custom Agilent 8x15K 60mer oligonucleotide microarrays (“RISET 2.0”) on the IOT cohort (training set) and on an independent cohort of patients from the ITN (USA) that contained similar groups of patients and included 23 tolerant recipients (“ITN samples”, test set). Set of genes were identified, whose expression on whole blood allowed the identification of 100% of the tolerant recipients in the training set and 84% in the test set. Keywords: classification of clinical samples, tolerance prediction IOT samples: 13 samples from 10 Tol-DF patients, 16 samples from 11 s-LP patients, 8 samples from 8 s-nCNI patients, 40 samples from 28 s-CNI patients, 10 samples from 9 CR patients, and 8 samples from 8 HC donors were analysed on a custom Agilent 8x15K 60mer oligonucleotide microarray encomprising 5069 probes in triplicates. The microarray is dedicated to transplantation research and was designed based on current literature and published and unpublished data provided by the RISET consortium. For the probe selection procedure we specially focused on the detection of multiple transcript variants of a gene, on optimized hybridization properties of the probes, and on the avoidance of crosshybridization. The sampling dates of replicate samples from the same patient range from one day to 1.5 years. ITN samples: 31 samples from 23 Tol-DF patients, 14 samples from 11 s-LP patients, 52 samples from 34 s-CNI patients, 25 samples from 18 CR patients, and 20 samples from 20 HC donors were analysed on the same microarray platform and served as test set. The samples of the two cohorts differ in the protocol of RNA preparation.

ORGANISM(S): Homo sapiens  

SUBMITTER: Rachel Hilton  Magdalena Krajewska   Jean-Paul Soulillou   Bettina Peters   Lawrence Turka   Kathryn J Wood   Cecile Braudeau   Uwe Janssen   Kasia Bourcier   Maria P Hernandez-Fuentes   Amany Ballow   Adnan Sharif   Kenneth Newel   Hans-Dieter Volk   Stephanie Chapman   Birgit Sawitzki   Pervinder Sagoo   Anthony N Warrens   Robert I Lechler   Ligia Craciun   Esperanza Perucha   Ruhena Sergeant   Vicki Seyfert-Margolis   Patrick Miqueu   Stefan Tomiuk   David A Stephens   Flavia Rovis   Michel Goldman   Ian Roberts   Magali Giral   Alain Le Moine   Graham Lord   Sophie Brouard   Elvira Jimenez    

PROVIDER: E-GEOD-14655 | ArrayExpress | 2010-05-25

SECONDARY ACCESSION(S): GSE14655PRJNA112341

REPOSITORIES: GEO, ArrayExpress

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Publications

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans.

Sagoo Pervinder P   Perucha Esperanza E   Sawitzki Birgit B   Tomiuk Stefan S   Stephens David A DA   Miqueu Patrick P   Chapman Stephanie S   Craciun Ligia L   Sergeant Ruhena R   Brouard Sophie S   Rovis Flavia F   Jimenez Elvira E   Ballow Amany A   Giral Magali M   Rebollo-Mesa Irene I   Le Moine Alain A   Braudeau Cecile C   Hilton Rachel R   Gerstmayer Bernhard B   Bourcier Katarzyna K   Sharif Adnan A   Krajewska Magdalena M   Lord Graham M GM   Roberts Ian I   Goldman Michel M   Wood Kathryn J KJ   Newell Kenneth K   Seyfert-Margolis Vicki V   Warrens Anthony N AN   Janssen Uwe U   Volk Hans-Dieter HD   Soulillou Jean-Paul JP   Hernandez-Fuentes Maria P MP   Lechler Robert I RI  

The Journal of clinical investigation 20100524 6


Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immu  ...[more]

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