Abstract: SA-PO0731
Mesenchymal Plasticity in Resident Renal Cells and Leukocytes Is Associated with Renal Pathology in Lupus Nephritis as Revealed by Imaging Mass Cytometry Proteomics
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
- Louis Sam Titus, Anto Sam Crosslee, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Tan, Ying, Peking University First Hospital, Beijing, China
- Romine, Haley Marie, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Appalaneni, Rohith, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Wang, Richard, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Saha, Pia, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Gadamsetty, Ronuk Dev, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Lindblom, Julius, Karolinska Universitetssjukhuset, Stockholm, Stockholm County, Sweden
- Xu, Yitian, Houston Methodist, Houston, Texas, United States
- Zheng, Junjun, Houston Methodist, Houston, Texas, United States
- Parodis, Ioannis, Karolinska Universitetssjukhuset, Stockholm, Stockholm County, Sweden
- Cai, Qi, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Chang, Anthony, The University of Chicago, Chicago, Illinois, United States
- Chen, Shu-Hsia, Houston Methodist, Houston, Texas, United States
- Zhao, Minghui, Peking University First Hospital, Beijing, China
- Mohan, Chandra, University of Houston Cullen College of Engineering, Houston, Texas, United States
Background
Using Imaging Mass Cytometry (IMC), we aim to study the molecular changes within lupus nephritis (LN) kidneys, that differentiate patients with low renal pathology indices (AI/CI) from patients with high renal pathology indices. We also investigate the occurrence of epithelial-mesenchymal plasticity in resident renal cells and infiltrating immune cells in LN biopsy samples.
Methods
35 plex-IMC was conducted on renal biopsies from 6 low AI/CI active LN, 3 high AI/CI active LN, and 3 minimal change disease (MCD) controls. After thresholding for noise reduction, image stacks were generated and analyzed using ImageJ.
Results
A significant increase in infiltrating immune cells (4-fold, p<0.01) was observed in high AI/CI LN compared to low AI/CI kidneys. Increased extracellular matrix (ECM) proteins (2-fold, p<0.001), such as Collagen I/IV and Fibronectin was observed in high AI/CI LN kidneys in glomerular and tubulo-interstitial regions (Fig. 1). Similarly, increased S100A4 and Vimentin were observed on podocytes, parietal epithelial cells, macrophages, T-cells and tubules in LN kidneys (Fig. 1). Finally, heightened HLA-DR expression, specifically on macrophages and glomerular endothelial cells in high AI/CI samples allude to enhanced antigen presentation in LN kidneys.
Conclusion
Spatial proteomics reveals that more severe renal pathology in LN is associated with extracellular matrix accumulation, mesenchymal plasticity and prolific immune cell infiltration.
Extracellular matrix buildup marks more severe pathology in LN. High vimentin and S100A4 expression was noted in podocytes(W), parietal epithelial cells(P) macrophages (M), tubules (T), CD4+ T-cells (4), memory T-cells (mT) and extra-glomerular endothelium (“E”) in LN. Shown data is representative of 35 ROIs from 9 active LN patients, and 3 MCD controls.