Recent work suggests that genes related to DNA replication signaling, RNA polymerase assembly, & pathogen recognition receptors are biomarkers for BKPyVN (Sigdel et al. Transplant 2016: 10: 2062). We have further examined this premise by performing RNA-seq analysis on 12 allograft and native kidney biopsies from patients who had no evidence of viral infection. RNA-seq was performed on on FFPE using the Invitrogen Pure Link FFPE tissue Total RNA Isolation Kit and the Ion Ampliseq Trancriptome Human Gene Expression Kit. Total RNA yields from 9 needle biopsies varied from 0.16 to 5.62 ug and generated 111-123 bp sequences. The mean sequence yield was 3.04E+07 ±1.13E+07 reads, of which 99.4% aligned to the human transcriptome. Differential RNA expression analysis using the DESeg program identified upregulation and down regulation of several genes in biopsy material. Genes believed to be differentially expressed in BKPyVN were found in the following diagnostic categories: (1) TCMR or T-cell mediated rejection (BST2, CCL2, F13A1, HSPD1, IFIT1, RARRES3; POLR21; C1QB; CXCL13, CXCL9); (2): inflamed areas of fibrosis/tubular atrophy or i-IFTA (AIF1, CD14, CD2, CD48, GPR183), (3) acute tubular injury (C3AR1, CD163, CLEC2B,CTSS, CYTIP), and (4) Interstitial nephritis in the native kidney (ADA, AIF1, CASP1, CCL19, CCL2). The top 5 pathways activated in the gene set that overlapped TCMR were Granulocyte Adhesion and Diapedesis ,Agranulocyte Adhesion and Diapedesis ,Pathogenesis of Multiple Sclerosis ,Role of IL-17F in Allergic Inflammatory Airway Diseases and LXR/RXR Activation. In conclusion, the search for virus specific molecular signatures is confounded by substantial overlap in pathogenetic mechanisms of tissue injury in BKPyVN and TCMR. A suggested approach to solving this problem is to organize collaborative multi-center studies using large data sets representing a very broad spectrum of transplant pathology including different stages in the evolution of BKPyVN.

CITATION INFORMATION: Pan L, Zeng G, Lyu Z, Huang Y, Randhawa P. The Search for a Polyomavirus BK Nephropathy (BKPyVN)-Specific Transcriptomic Signature. Am J Transplant. 2017;17 (suppl 3).

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