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Kidney Week

Abstract: FR-PO870

The Molecular Profile in Kidney Allograft Highlighting Subclinical Acute Rejection (SAR): Towards a Targeted Treatment

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Cox, Sharon N., University of Bari, Bari, Italy
  • Chiurlia, Samantha, Schena Foundation, Valenzano, Bari, Italy
  • Schena, Francesco Paolo, University of Bari, Bari, Italy

Group or Team Name

  • The Italian Transplantomics Group
Background

SAR diagnosed by protocol biopsy is an independent risk factor for chronic allograft injury. We organized a molecular study on 24 AB0 compatible cadaveric kidney transplant recipients with standard immunological risk who received protocol biopsy in the first post-transplant year. Aim of our study was to identify specific gene expression changes that characterize SAR and to highlight specific therapeutic interventions based on the molecular fingerprints.

Methods

Total RNA was extracted from archival FFPE renal tissue samples of 12 patients with SAR scored by 2 pathologists according to the updated Banff criteria and a control group of 12 patients with normal histological findings in protocol biopsies performed at 3- and 12-months post-transplant. All patients had a stable renal function (mean serum creat < 1.65 mg/dL). The cRNA fragments were hybridized on GeneChips Agilent. Genome-wide gene expression profiles were generated and bioinformatic analysis was done with Genespring. A false discovery rate (FDR) <0.02 and fold change > 2 were applied. Canonical pathways and biological functions were explored using Ingenuity pathway analysis (IPA) software. Real Time PCR was used for validation of the identified transcripts.

Results

We identified 1849 genes aberrantly modulated in SAR biopsies, 184 were down-regulated and 1257 up-regulated. Three-dimensional Principal Component Analysis showed a different spatial distribution between the SAR patients and control Patients. The most significant canonical pathways were Natural killer cell signalling (p=0.00413), Wnt/β-catenin pathway (p=0.03) Role of cytokines in mediating communication between immune cells (p=0.04). The top selected networks highlighted several modulated genes involved in Acute Kidney Injury and candidate transcripts were validated by qRT-PCR.

Conclusion

Our data demonstrates a specific fingerprint associated with SAR characterized by various genes involved in molecular inflammatory processes and crosstalk between immune cells. These results suggest the possibility of early recognition and targeted treatment before chronic allograft disease.

Funding

  • Government Support - Non-U.S.