MO051: Single-Cell Transcriptomics of Lupus Nephritis with ANCA Positive
Nephrology, Dialysis and Transplantation
BACKGROUND AND AIMS Lupus nephritis (LN) is one of the most common complications of SLE that can lead to worsened kidney function or renal failure. Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies that are against antigens in the cytoplasm of neutrophils and monocytes and can lead to an autoimmune disease characterized by vascular necrotizing inflammation. The presence of ANCA in serum can also be found in SLE. Positive ANCA serology in patients with LN is associated with
... histopathologic features on renal biopsy and seems to affect outcome of LN. Deeper understanding of the molecular pathogenesis in LN with ANCA positive is needed to identify novel targets improve the outcome of LN. METHOD Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from one LN patient with PR3-ANCA positive and a healthy adult kidney. We identified distinct cell clusters through unsupervised clustering analysis. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. RESULTS Unsupervised clustering analysis identified 15 distinct cell types including all of the renal intrinsic cells and major immune cells. The DEGs in kidney endothelial cells and intercalated cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling and Th17 cell differentiation. Macrophages displayed increased expression of HLA-DRB5, which plays a central role in the immune system by presenting peptides derived from extracellular proteins. TYROBP, a gene plays a role in signal transduction and inflammation, was also high-expressed in macrophages from kidney of LN with PR3-ANCA positive. The receptor-ligand crosstalk analysis highlighted the interactions between endothelial cells and other cells in LN, which infers great importance in LN. CONCLUSION We provide a searchable resource of single-cell RNA sequencing to LN with PR3-ANCA positive to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis and offer new insight into therapeutic targets of this unique type of LN.