Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Polyomavirus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. Microscopic observations of PVAN are similar to T-cell mediated rejection (TCMR), with unclear underlying molecular mechanisms.
To identify PVAN-specific gene expression we analyzed 60 demographically matched samples from a set of microarray data collected on 162 kidney biopsies (15 PVAN, 15 TCMR and 30 controls (NL)) for global gene expression. Data and pathway enrichment analysis was performed using GO-Elite, AltAnalyze and LineageProfiler. Gene expression data were confirmed by qRT-PCR and at the protein level using immunohistochemistry (IHC).
Unsupervised hierarchical clustering analysis of all 162 biopsies revealed high similarity between PVAN and TCMR gene expression as compared to NL. The case-control study of 60 patients confirmed the great overlap of probesets (958) differentiating PVAN and TCMR vs NL that were evident in the KEGG database, Gene Ontology, along with specific computationally inferred immune cell markers. Increasing the stringency for the specificity (p <0.001 and >2-fold expression) between PVAN and TCMR, 209 and 245 unique PVAN and TCMR injury-specific probesets were found, respectively. While TCMR-specific probeset were basically involved in costimulation (CTLA4, CD28, CD86) and TCR signaling (NFATC2, LCP2), PVAN-specific probesets were mainly related to viral replication process (IFITM1, LTF, RARRES3), RNA polymerase assembly (POLR2l, TAF10) and pathogen recognition receptors (C1QA, CFD). A principal component analysis using these genes further confirmed the most optimal separation between the different 3 clinical phenotypes. Validation of 5 PVAN-specific probesets (RPS15, CFD, NOSIP, LTF and IFITM1) by RT-PCR and further confirmation by IHC of 2 PVAN-specific proteins with anti-viral function (LTF and IFITM1) was done, showing significantly higher expression in PVAN as compared to TCMR and NL kidney biopsies.
Even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, particular PVAN-specific transcripts are differentially expressed, some of them encoding for molecules with well-known anti-viral properties.
To cite this abstract in AMA style:Sigdel T, Bestard O, Salomonis N, Hsieh S-C, Naesens M, Torras J, Tran T, Roedder S, Sarwal M. Perturbation of Polyomavirus Nephropathy-Specific Gene Expression in Kidney Allografts [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/perturbation-of-polyomavirus-nephropathy-specific-gene-expression-in-kidney-allografts/. Accessed August 6, 2020.
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