Abstract: SA-PO0730
Spatial Proteomics Reveals Significant Bowman Capsule Breach and Podocyte Loss in Lupus Nephritis, Associated with Heightened Histological Activity and Chronicity
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
- Appalaneni, Rohith, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Pisati, Akanksha Reddy, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Srinivasan, Vishal Akash A, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Romine, Haley Marie, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Nguyen, Angela Vu, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Truong, Luan D., Houston Methodist, Houston, Texas, United States
- Mohan, Chandra, University of Houston Cullen College of Engineering, Houston, Texas, United States
Background
Recent studies suggest Bowman’s capsule breach (BCB) may be a marker of glomerular injury in LN, but its quantitative role in disease progression remains unclear. Here, we explore the interplay between glomerular structural integrity and the changes in cellular composition of the glomerulus and renal histopathological indices.
Methods
Spatial proteomics was performed on 6 LN and 6 transplant control biopsies by cyclic immunofluorescence. BCB was quantified by breaks in continuity in Collagen IV staining and the numbers of resident glomerular cells and immune cells were quantified using QuPath, Python, and MATLAB.
Results
BCB was significantly more prevalent in LN (62% LN glomeruli vs 6% control glomeruli), with BCB percentages correlating positively with renal pathology scores (AI: r = 0.93, CI: r = 0.67) (Fig. 1). Glomeruli with high BCB also exhibited significantly more crescents, sclerosis, and interstitial fibrosis. Podocyte loss was pronounced in glomeruli with extensive BCB, associated with immune cell infiltration (M1/M2 macrophages and T cells), with M1 macrophages showing the strongest correlation.
Conclusion
Our study identifies BCB as a quantifiable, disease-relevant marker in LN. Its correlation with AI/CI scores, immune cell infiltration, and podocyte loss suggests a critical role in disease progression. Ongoing studies are aimed at understanding the triggers of glomerular capsule breach in LN, and its mechanistic consequences.
Figure 1. Glomeruli in various stages of BCB as indicated by Collagen IV expression.
Representative images of histopathology and collagen IV-pseudocolored spatial proteomic images of LN glomeruli in various stages of BCB. A total of 89 glomeruli from 6 healthy controls, 3 LN low AI/CI cases and 3 LN high AI/CI cases were examined. Based on the expression profile of collagen IV, the percentage BCB was calculated and correlated with renal histopathology scores.