Abstract: TH-PO544
Comparing Different Pathogenic Patterns Between Immunoglobulin A Nephropathy and Lupus Nephritis Using Integrated Bioinformatics Analysis
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Zhang, Haidong, Department of Nephrology, Peking University Third Hospital, Beijing, China
- Wang, Yue, Department of Nephrology, Peking University Third Hospital, Beijing, China
- Deng, Zhenling, Department of Nephrology, Peking University Third Hospital, Beijing, China
Background
Immunoglobulin A nephropathy (IgAN) and lupus nephritis (LN) are the most common primary and secondary glomerular diseases, respectively, sharing several similarities in clinical presentations. Common pathogenic mechanisms in IgAN and LN have been well established by previous studies. However, it is confusing how these two independent diseases carrying distinct pathological features are manifested considering the similarities between them. Therefore, different mechanisms of the pathogenesis between IgAN and LN were compared in this study.
Methods
Glomerular gene expression profiling data were acquired from the Gene Expression Omnibus (GEO) database. R packages were used for the data processing. Least Absolute Selection and Shrinkage Operator (LASSO) regression analysis and multivariate logistic regression analysis were used to construct models predicting IgAN and LN. Cibersort processed the analysis of immune cell infiltration in IgAN and LN. RT-qPCR was used to validate the gene expression in the human renal mesangial cells (HRMC).
Results
In the regressing predicting models based on differentially expressed genes (DEG) and weighted correlation network analysis (WACNA), retinoic acid receptor γ (RARG) and prolactin releasing hormone (PRLH) were independent risk factors for IgAN, and HECT domain and RCC1-like domain-containing protein 5 (HERC5) and interferon stimulated exonuclease gene 20 (ISG20) were independent risk factors for LN. GO analysis revealed that DEGs mostly correlated to IgAN in the “salmon” module in WGCNA were enriched in ligand-receptor activity induced cellular growth and development, and DEGs mostly correlated to LN in the “red” module were enriched in nucleic acid/nucleotide binding-induced type I interferon related activity and response to virus infection. Immune infiltration analysis showed CD4+ T-cells and M2 macrophage abundance in the glomerular compartment in IgAN and LN, respectively. The expression of RARG in HRMC was significantly elevated after stimulation of immune complexes (IC) from IgAN patients, staphylococcus aureus cell protein C (SAC) and interleukin 6 (IL-6).
Conclusion
IgAN and LN carry distinct molecular patterns in the pathogenesis, in which overexpression of RARG might be responsible for mesangial proliferation in IgAN.