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Abstract: SA-PO939

Single-Cell RNA Sequencing Reveals Immune Cell-Specific Genes and Pathways Associated with IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Wang, Le, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Zeng, Honghui, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Xiao, Yi, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Luo, Siweier, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Yang, Xiaoqiang, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Zhou, Yiming, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
Background

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN pathogenesis are still largely unclear. Single-cell RNA-sequencing is a high-throughput sequencing technology with cells as minimal units, which could be applied to explore the pathogenesis of IgAN.

Methods

Peripheral venous blood samples were collected from 6 healthy controls and 10 newly diagnosed IgAN patients. Peripheral blood mononuclear cells (PBMCs) were isolated by FACS sorting with above 80% cell viability. Then single cell RNA-sequencing was performed using the BD Rhapsody platform. Downstream analysis was performed with the Seurat V3.0. Meanwhile, the clinical data of the IgAN patients were co-analyzed with single-cell RNA-sequencing results.Experimental and research procedures were approved by and in accordance with the internal review board and human subject guidelines of the Sun Yat-sen Memorial Hospital and Sun Yat-sen University.

Results

First, we generated an single immune cell landscape of early IgAN. The differentially expressed genes (DEGs) between the control and IgAN groups were mainly related to the NK cell-mediated cytotoxicity and NK cell killing pathways. We found that significant decreases in the NK cell numbers and cytotoxicity genes. Interestingly, we discovered that NK cell numbers and marker genes were negatively correlated with many clinical parameters, including urinary protein creatinine ratio (UPCR) and serum galactose-deficient IgA1 and IgA. In contrast, DEGs of B cells were enriched in different viral infection pathways, and one specific B cell subgroup exhibiting the inhibition of NFκB signaling, was positively correlated with IgAN clinical parameters. In addition, a subpopulation of monocytes expressing interferon-inducing genes was positively associated with clinical severity of IgAN. Finally, we identified vast dynamics in intercellular communications of NK cells and monocytes in IgAN.

Conclusion

We constructed a landscape of peripheral blood mononuclear cells from early IgAN patients by using scRNA-seq and found significant alterations in the number and gene expression pattern of immune cells, some of which are closely related to clinical manifestations.