Abstract: SA-PO0958
Proteomic Profiling of Complement Components in Glomerular Diseases
Session Information
- Pathology: Updates and Insights
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Caza, Tiffany, Arkana Laboratories, Little Rock, Arkansas, United States
- Storey, Aaron J., Arkana Laboratories, Little Rock, Arkansas, United States
- Hassen, Samar, Arkana Laboratories, Little Rock, Arkansas, United States
- Edmondson, Ricky D., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Herzog, Christian, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
Background
The complement system plays a central role in glomerular disease development and resolution. Currently, renal biopsies assess the presence of complement through limited immunofluorescence stains (C3 and C1q). With more than 50 total proteins and fragments involved in the complement cascade, this method offers a severely restricted view into the mechanisms of tissue injury orchestrated by complement activation. A more comprehensive evaluation of complement components will advance the understanding of complement involvement in glomerulonephritis by allowing for multiplex detection of complement cascade proteins and activation products, which can be achieved by mass spectrometry.
Methods
Data-independent acquisition mass spectrometry was performed following extraction of proteins from tissue lysates, microdissected glomeruli, or protein G immunoprecipitates from residual kidney biopsy tissue. Cohorts included kidney biopsies from patients with lupus nephritis, membranous nephropathy, diabetic glomerulosclerosis, C3 glomerulonephritis, and controls.
Results
Abundances of complement components by mass spectrometry correlated with immunofluorescence intensity of C1q on kidney biopsies. Increased abundances of complement classical, lectin, final common pathway, and regulatory proteins correlated with disease activity in lupus nephritis, with increased abundance in patients with diffuse proliferative lupus nephritis compared to mesangial proliferative disease. Patients with the same disease state could be stratified on the basis of complement protein abundances in diabetic nephropathy and various types of proliferative glomerulonephritis. Finally, complement proteins and their activation products can be mapped to determine which components are impacted among individuals and between disease states.
Conclusion
Complement proteins and some of their split products can be reliably measured by mass spectrometry of kidney biopsies, which can enhance our understanding of complement-mediated tissue injury and heterogeneity in glomerular diseases.