Abstract: TH-PO547
Energy Score Analysis in Immune Cells Linked to Atypical Hemolytic Uremic Syndrome Using Single-Cell Sequencing
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Chen, I-Ru, China Medical University Hospital Department of Internal Medicine, Taichung, North, Taiwan
- Tu, Siang-Jyun, China Medical University Hospital, Taichung, Taiwan
- Huang, Chiu-Ching, China Medical University Hospital Department of Internal Medicine, Taichung, North, Taiwan
- Lai, Ping chin, China Medical University Hospital Department of Internal Medicine, Taichung, North, Taiwan
Background
Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) with complex genetic and immunologic factors. Our single-cell sequencing shows a significant correlation between aHUS and immune cell subsets. Energy metabolism is crucial for immune responses, with cells reprogramming upon activation. We hypothesize that energy metabolism genes play a role in aHUS pathogenesis. This study evaluates energy metabolism-related gene expression (Energy Score, ES) in immune cell subpopulations from aHUS patients, unaffected family members, and healthy controls, enabling detailed comparison of aHUS activity and new research avenues.
Methods
We recruited 13 aHUS patients, three unaffected families, and four healthy controls from a medical center in Taiwan. Peripheral blood samples underwent single-cell RNA sequencing (scRNA-seq). The aHUS patients were classified into stable and unstable groups. ScRNA-seq data were processed with CellRanger and analyzed using Seurat in R. Inflammatory genes from the Molecular Signatures Database (MSigDB) were used to compute the energy score (ES) with Seurat's AddModuleScore, enabling detailed analysis of cellular energy metabolism.
Results
Our study assessed Energy Score (ES) in cell subpopulations among aHUS patients, aHUS nuclear families without the syndrome, and healthy controls via transcriptomic analysis. Intermediate monocytes showed the highest ES in aHUS patients, followed by aHUS families, and then healthy controls, with significant differences (p < 0.0001). No significant differences were found between aHUS families and healthy controls. Subclusters 1 and 2 of intermediate monocytes had significantly higher ES in aHUS patients compared to others. ES in intermediate monocytes, naïve CD8 T cells, terminal effector CD8 T cells, and non-V delta 2 gamma delta T cells was highest in unstable aHUS patients, followed by stable aHUS patients, aHUS families, and healthy controls.
Conclusion
Our study reveals a link between energy metabolism genes and aHUS severity through single-cell sequencing energy scores. Intermediate monocytes are significant markers of aHUS activity. This suggests energy metabolism genes play a key role in aHUS, warranting further research. These findings could predict disease stability and inform new therapeutic approaches.