Abstract: SA-PO0720
Serum Lipid-Proteome Profiling Unveils Metabolic-Immune Dysregulation in IgAN
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Wang, Gangan, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- Zheng, Ke, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- Li, Xuemei, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Background
IgA nephropathy (IgAN), the most common glomerulonephritis, is driven by galactose-deficient IgA1 (Gd-IgA1) deposition, leading to progressive kidney injury. Limited therapies and unclear mechanisms of immune-metabolic crosstalk prompted this multi-omics study to unravel lipid-protein interactions in IgAN pathogenesis.
Methods
IgAN patients (biopsy-confirmed, Oxford MEST-C) and healthy controls underwent serum lipidomics (HPLC-QTRAP 6500+) and proteomics (LC-MS/MS). Bioinformatics included limma-based differential analysis, pathway enrichment (Wikipathway/Reactome), and lipid-protein networks.
Results
1.Lipid Dysregulation:
↑TGs (P<0.001), DGs, NeuAcHex2Cer; ↓LPAs (P<0.01), FFAs.
Hyperlipidemia (↑TG, ↓HDL) and renal dysfunction (↓eGFR, ↓Alb).
2.Proteome Alterations:
Upregulated: VEGFA-VEGFR2 (*FDR=0.002*) – endothelial leakage.
Downregulated: Galactose metabolism (*FDR=0.01*), NRF2. ↑GALK1/↓PGM1 implicates dysregulated galactose disposal.
3.Correlations:
TGs: Linked to neutrophils (ρ=0.62), blood pressure, urine SG.
LPAs: Associated with eGFR (ρ=0.71), serum Alb.
Neutrophil Suppression: ↓HEXB/PRCP (P<0.05); TG/LPA-correlated proteins enriched in neutrophil degranulation (*FDR=0.005*).
Conclusion
Systemic TG-LPA imbalance impairs neutrophil-mediated IC clearance, while VEGFA-VEGFR2 exacerbates endothelial leakage. Serum TG/LPA ratios and HEXB/PRCP are potential biomarkers for IC persistence. Targeting lipid profiles (e.g., TG-lowering) may mitigate IgAN progression.
Figure 1. Lipidomics and proteomics analyses of the systemic microenvironment of IgAN based on serum profiles of IgAN and HC
Figure 2. Differentially expressed serum TGs and LPAs functionally converge on neutrophil function
Funding
- Government Support – Non-U.S.