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Discovery of novel differentially expressed genes related to interstitial fibrosis and tubular atrophy among kidney transplantation recipients by mRNA-sequencing

ABSTRACT: Discovery of novel differentially expressed genes related to interstitial fibrosis and tubular atrophy among kidney transplantation recipients by mRNA-sequencing

PROVIDER: PRJNA901985 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22302605_1.fastq.gz	Fastqsanger.gz
	SRR22302605_2.fastq.gz	Fastqsanger.gz
	SRR22302606_1.fastq.gz	Fastqsanger.gz
	SRR22302606_2.fastq.gz	Fastqsanger.gz
	SRR22302607_1.fastq.gz	Fastqsanger.gz

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Project description:Rationale: Interstitial fibrosis and tubular atrophy (IFTA) is found in ~25% of 1-year biopsies post-transplant(1, 2). It correlates with decreased graft survival when histological evidence of inflammation is present¬.(3-5) Identifying the etiology of IFTA is important because longterm graft survival has not changed as expected given improved therapies and a dramatically reduced incidence of acute rejection.(6-8) Methods: Gene expression profiles of 234 samples were obtained with matching clinical and outcome data (7 transplant centers). 81 IFTA samples were divided into subphenotypes by the degree of inflammation on histology: IFTA with acute rejection (AR), IFTA with inflammation and IFTA without inflammation. Samples with AR (n=54) and normally functioning transplants (TX; n=99) were used in comparisons. Conclusions: Gene expression profiling of all IFTA phenotypes were strongly enriched for cAR gene dysregulation pathways, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. We also found that the relative expression of AR-affiliated genes correlated with future graft loss in IFTA samples without inflammation. We conclude that undetected and/or undertreated immune rejection is leading to IFTA and graft failure. RNA was extracted from biopsy samples using the RNEasy kit (Qiagen), biotinylated cRNA prepared using Ambion MessageAmp Biotin II and hybridized to Affymetrix HG U133 Plus PM peg arrays (http://affymetrix.com/index.affx). Probe intensity data were log2–transformed and normalized using a custom-designed frozen Robust Multichip Average (fRMA). Low-variance and low signal probes were filtered according to industry standards, resulting in a filtered gene list with 17,564 transcripts. This dataset is part of the TransQST collection.

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Discovery of novel differentially expressed genes related to interstitial fibrosis and tubular atrophy among kidney transplantation recipients by mRNA-sequencing

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