Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) based studies have suggested that BKPyVN leads to the excretion of virus-specific urinary peptides which can serve as diagnostic markers of this disease in kidney transplant patients (Sigdel et al. Kid Int 2016:89:1244). We have used RNA-seq to investigate the presence of the corresponding proteins in a series of 12 allograft and native kidney biopsies from patients who had no evidence of viral infection. RNA-seq was performed on FFPE using the Invitrogen Pure Link FFPE tissue Total RNA Isolation Kit and the Ion Ampliseq Trancriptome Human Gene Expression Kit. Proteins/peptides reported to be differentially expressed in BKPyVN were found in the following diagnostic categories: (1) 56 in TCMR or T-cell mediated rejection (DNASE1, RPL18, SNCG, PLG, CXCL12, LTBP1, LMAN2, IGKC, CPXM1, CRABP2 & others ); (2):42 in inflamed areas of fibrosis/tubular atrophy or i-IFTA (DNASE1, LTF, LTBP1, COL12A1, DES, C7/8A, plasminogen, PLG, PRSS3 & others), (3) 69 in acute tubular injury (KRT1/77, HSPA5, CXCL12, DES, DKK3, C7/8A, CFB, keratins 1/77 LDHC & others), (4) 34 in interstitial nephritis in the native kidney (CFB, HSP90AB2P, IGHM, KASALD1, PI3, SERPINA1/3, SERP4/5, and 23 others that overlapped the TCMR group. It is of interest to note that biopsies with TCMR show expression of genes belonging to the complement, immunoglobulin, and blood coagulation pathways. The top 16 pathways upregulated in biopsies upregulated in biopsies with TCMR is shown in Figure 1. Conclusions: Development of a valid LC-MS/MS based diagnostic tool for BKPyVN needs further rigorous studies of sensitivity and specificity. Moreover, proteomics based analyses generate candidate molecules which are quite different from those discovered by transcriptomics analyses, stressing the need for additional correlative studies using multiple investigative tools.

CITATION INFORMATION: Zeng G, Pan L, Lyu Z, Huang Y, Randhawa P. Lack of Specificity of LC-MS/MS Based Urinary Biomarkers for Polyomavirus BK Nephropathy (BKPyVN). Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress