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Expression of the IL-17/Th17 axis in the development of acute renal allograft rejection

ABSTRACT: Genesets for the IL-17 pathway and Th17 T-helper cell subtype showed increasing enrichment in 33 pre-transplant donor biopsies and 33 matching post-transplant biopsies from patients with increasing Banff grades of acute rejection (no signficant abnormalities, n=17; borderline, n=4; ARIA, n=7; ARIB, n=6) in gene set analysis using SAM (GSA, FDR 0.5; 1000 permutations, log rank regression) for a total of 3307 publically available and manually curated gene-sets. 14 genes of the IL-17 pathway gene-set and 132 genes of the Th17 gene set segregated patients according to their histological diagnosis by unsupervised hierarchical clustering and principal component analysis. This study demonstrates a significant role for the IL-17 pathway in the development of acute renal allograft rejection. Therapeutically targeting the IL-17 pathway presents a promising option in transplantation medicine and can be acchieved through drug reposittioning. Keywords: IL-17 pathway, drug repositioning, gene set enrichment analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE34437 | GEO | 2014/01/01

SECONDARY ACCESSION(S): PRJNA149613

REPOSITORIES: GEO

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Expression of the IL-17/Th17 axis in the development of acute renal allograft rejection

Project description:Genesets for the IL-17 pathway and Th17 T-helper cell subtype showed increasing enrichment in 33 pre-transplant donor biopsies and 33 matching post-transplant biopsies from patients with increasing Banff grades of acute rejection (no signficant abnormalities, n=17; borderline, n=4; ARIA, n=7; ARIB, n=6) in gene set analysis using SAM (GSA, FDR 0.5; 1000 permutations, log rank regression) for a total of 3307 publically available and manually curated gene-sets. 14 genes of the IL-17 pathway gene-set and 132 genes of the Th17 gene set segregated patients according to their histological diagnosis by unsupervised hierarchical clustering and principal component analysis. This study demonstrates a significant role for the IL-17 pathway in the development of acute renal allograft rejection. Therapeutically targeting the IL-17 pathway presents a promising option in transplantation medicine and can be acchieved through drug reposittioning. Keywords: IL-17 pathway, drug repositioning, gene set enrichment analysis A total of 66 human renal allograft protocol biopsies were included in this study, 33 biopsies obtained at implantation prior to revascularization and 33 protocol biopsies obtained after transplantation. Whole genome expression profiles were assessed using microarrays. This dataset is part of the TransQST collection.

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