title: Analysis of independent microarray datasets of renal biopsies identifies a robust transcript signature of acute allograft rejection.
abstract: Transcriptomics could contribute significantly to the early and specific diagnosis of rejection episodes by defining 'molecular Banff' signatures. Recently, the description of pathogenesis-based transcript sets offered a new opportunity for objective and quantitative diagnosis. Generating high-quality transcript panels is thus critical to define high-performance diagnostic classifier. In this study, a comparative analysis was performed across four different microarray datasets of heterogeneous sample collections from two published clinical datasets and two own datasets including biopsies for clinical indication, and samples from nonhuman primates. We characterized a common transcriptional profile of 70 genes, defined as acute rejection transcript set (ARTS). ARTS expression is significantly up-regulated in all AR samples as compared with stable allografts or healthy kidneys, and strongly correlates with the severity of Banff AR types. Similarly, ARTS were tested as a classifier in a large collection of 143 independent biopsies recently published by the University of Alberta. Results demonstrate that the 'in silico' approach applied in this study is able to identify a robust and reliable molecular signature for AR, supporting a specific and sensitive molecular diagnostic approach for renal transplant monitoring.
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mezard
authors.forename: Céline C
authors.initials: CC
authors.lastname: Berthier
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
authors.forename: Sergio
authors.initials: S
authors.lastname: Kaiser
authors.forename: Martin
authors.initials: M
authors.lastname: Schumacher
authors.forename: Grazyna
authors.initials: G
authors.lastname: Wieczorek
authors.forename: Marc
authors.initials: M
authors.lastname: Bigaud
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kehren
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Friedrich
authors.initials: F
authors.lastname: Raulf
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Marti
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000502:physiology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D014184:Transplantation, Homologous; D055815:Young Adult