MO242: Intrarenal Single Cell Sequencing of Hepatitis B Virus Associated Membranous Nephropathy

Abstract

Abstract BACKGROUND AND AIMS The pathogenesis underlying hepatitis B virus (HBV)-associated membranous nephropathy (MN) remains incompletely understood. METHOD To decipher the etiopathogenesis of HBV-associated MN, intrarenal single-cell RNA sequencing (scRNA-seq) was applied to the kidney biopsy from a HBV-associated MN patient and a health control to define the transcriptomic landscape at single-cell resolution. Differentially expressed genes (DEGs) and enrichment analysis were compared between HBV-associated MN and anti-PLA2R positive idiopathic membranous nephropathy (IMN) using intrarenal scRNAseq. RESULTS We generated 4114 intrarenal single-cell transcriptomes from a HBV-associated MN patient by single-cell RNA-sequencing. We found that kidney podocytes cells in the HBV-associated MN patient displayed increased expression of several genes, including EDIL3, GPC6, HSPA5 and CTGF, which were closely related to extracellular matrix formation. Kidney endothelial cells of HBV-associated MN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, NOD-like receptor signaling, NF-kappa B signaling pathway and Toll-like receptor signaling pathway. TNF signaling pathway and IL-17 signaling pathway activation were confirmed in proximal tubule cells from the HBV-associated MN patient. Moreover, ligand-receptor analysis highlighted the extensive communication of mesangial cells, which infers great importance in HBV-associated MN. Furthermore, gene ontology (GO) function enrichment analysis revealed that DEGs of endothelial cells from the HBV-associated MN patient were enriched in interleukin-6 secretion and interleukin-1 secretion when compared with anti-PLA2R positive IMN. CONCLUSION These results offer new insight into the pathogenesis of HBV-associated MN.