2010 - Transplantomics and Biomarkers in Transplantation


PREDICTING GRAFT RISK BY TRANSPLANTOMICS

3.3 - MICRORNA AND RNA PROFILES WITH GRAFT REJECTION

Presenter: Dany, Anglicheau, Paris, France
Authors: Dany Anglicheau


MICRORNA AND RNA PROFILES WITH GRAFT REJECTION
Dany Anglicheau, Associate Professor, Kidney Transplant Unit, Necker Hospital, Paris, France
Learning Objectives:
1. Learn a framework for developing microRNA as new biomarkers of kidney allograft outcome.
2. Discuss the implication of miRNAs as new biomarkers of allograft rejection.
3. Gain an understanding of the application of urinary cell mRNA levels as markers of IFTA and graft outcome.
The overall objective of this talk is to present new biomarkers of acute T-cell mediated rejection of the kidney allograft and of interstitial fibrosis/tubular atrophy, the hallmark of chronic allograft nephropathy, by the analysis of microRNA (miRNA) or messenger RNA (mRNA) profiles in biopsy samples or urinary cells.
We have identified a molecular signature of acute rejection based on a high throughput miRNA quantification of kidney allografts. Our investigation identified a subset of 17 miRNAs that are differentially expressed in acute rejection biopsies compared to normal allograft biopsies at a P-value < 0.01, and the presence or absence of acute rejection could be accurately predicted using miRNA expression patterns. The identification of differentially expressed miRNAs during an episode of acute rejection could lead to the development of new non-invasive biomarkers.
Through the analysis of mRNA expression levels in urinary cells, we have recently developed new hypothesis-driven mRNA biomarkers that can noninvasively diagnose interstitial fibrosis/tubular atrophy. In addition, a combination of mRNAs involved in epithelial-to-mesenchymal transition/fibrogenesis and alloimmune response appeared predictive of the subsequent function of kidney allograft with normal histology.


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