Session Time: 6:00pm-7:00pm
Presentation Time: 6:25pm-6:30pm
*Purpose: Late stage BKVN can show C4d as well as classic immune complex deposits in the tubular basement membranes (Bracamonte et al. Am J Transplant 2007: 7: 152: Batal et al. Modern Pathology 2012: 43: 69). A comprehensive study of the role of complement in the pathogenesis of BKVN has not been performed.
*Methods: RNA-seq, Tandem mass tag (TMT) isobaric labeling and label free quantitative profiling were used to interrogate a set of 15 allograft biopsies with equal representation of stable graft function (STA), healthy kidney (HKD), and BKVN. Data analysis consisted of reporter ion intensity relative quantification, log transformation, quantile normalization, and differential expression (DE) analysis by the R package “limma”.
*Results: In RNAseq data, 6201 genes were differentially expressed between BKVN and stable biopsies (p<0.05). This dataset was intersected with 326 human complement related genes downloaded from the European Bioinformatics Institute (EBI) website. This resulted in the identification of 44 genes associated with positive regulation of classical pathway (IGHM, IGHG1, IGHA1) or alternate pathway (CFD, a C3 proactivator convertase), and negative regulation of both the classical and lectin pathways (SERPING1 or C1-inhibitor). To date, 5 genes in the RNA-seq data have been validated by TMT or label free proteomics analysis. Immunoglobulin gene expression provides evidence for antibody-antigen complex driven activation of the classical complement pathways. Complement factor D (CFD) cleaves factor B to a noncatalytic chain Ba and a catalytic chain Bb. The active subunit Bb associates with C3b to form the alternative pathway C3 convertase. C1-inhibitor irreversibly binds to and inactivates C1r and C1s proteases in the C1 complex of classical pathway, as well as the MASP-1 and MASP-2 proteases in the MBL complexes of the lectin pathway.
*Conclusions: Complement proteins play a role in the pathogenesis of virus mediated tissue injury in BKVN. This observation opens up the possibility of exploring anti-complement therapies in a subset of patients with C4d staining or immune complex deposits in the tubular basemen.
To cite this abstract in AMA style:Randhawa P, Fei F, Huang Y, Tseng G, Xiao K. Transcriptomics and Proteomics Profiling of Complement Pathway (cp) Proteins in Biopsies With Polyomavirus Bk Nephropathy (bkvn) [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/transcriptomics-and-proteomics-profiling-of-complement-pathway-cp-proteins-in-biopsies-with-polyomavirus-bk-nephropathy-bkvn/. Accessed July 24, 2021.
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