Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: 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. A control group of 12 patients with normal histological findings in protocol biopsies performed at 3- and 12-months post-transplant was used. All patients had a stable renal function (mean serum creat < 1.65 mg/dL). The cRNA fragments were hybridized on Agilent GeneChips. Genome-wide gene expression profiles were generated and bioinformatic analysis was done with Genespring GX 14.9. A false discovery rate (FDR) <0.02 and fold change > 2 were applied. To assess biological relationships among genes, we used the Ingenuity Pathway Analysis software. Real time PCR was used for the validation of the identified transcripts and Immunohistochemistry is being used for protein validation.
*Results: We identified 1849 genes aberrantly modulated in SAR biopsies, 184 were down-regulated and 1257 up-regulated (FC>2 and FDR corrected p value <0.02). Three-dimensional Principal Component Analysis showed a different spatial distribution between SAR patients and control Patients. Furthermore, the most significant canonical pathways were Natural killer 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 network highlighted several modulated genes involved in Acute Kidney Injury (NFKBIZ, SLAMF8, CD247 and TNFSF14) and these candidate transcripts were validated by qRT-PCR. Protein validation is underway.
*Conclusions: Transcriptomics on FFPE renal biopsies with long-term follow-up, offers the possibility to detect genes involved in SAR that may be responsible for chronic allograft failure. Our study shows a specific fingerprint associated with SAR characterized by various validated 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.
To cite this abstract in AMA style:Cox SN, Chiurlia S, Schena FP. The Molecular Profile of Kidney Allografts Unveil Specific Biomarkers for Subclinical Acute Rejection (SAR). Towards an Early Detection and a Targeted Treatment [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/the-molecular-profile-of-kidney-allografts-unveil-specific-biomarkers-for-subclinical-acute-rejection-sar-towards-an-early-detection-and-a-targeted-treatment/. Accessed October 27, 2020.
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