Abstract: FR-PO0852
Proteomic Identification of Serum Effectors of Neutrophil Activation in Lupus Nephritis
Session Information
- Glomerular Diseases: Practice and New Concepts Shaping Modern Care
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Cummins, Timothy, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Samuelson, David J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Tandon, Shweta, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Nagane, Siyona S., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Rane, Madhavi J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Barati, Michelle T., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Caster, Dawn J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Powell, David W., University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
A primary mechanism by which neutrophils kill bacteria is degranulation-mediated release of antimicrobial proteins. Uncontrolled release of these toxic compounds results in tissue injury. An important contribution of neutrophil degranulation in lupus nephritis (LN) is established. Our recent report shows that degranulation is enhanced in untreated LN patient neutrophils and that serum from active LN patients stimulates degranulation in neutrophils from healthy donors (HD). We hypothesize that inflammatory injury in LN is driven by specific serum proteins that activate neutrophil degranulation leading to pathological outcome. The aim of this study was to empoy protein fractionation combined with mass spectrometry-based proteomics to identify candidate effectors of neutrophil degranulation in serum from LN patients with active disease compared with remission.
Methods
Pooled serum samples from 4 LN patients with active disease (UPCR >500 mg/g) or follow-up inactive status (< 500 mg/g) and HD were separated by size exclusion chromatography and protein fractions from each sample group were applied to neutrophil degranulation assays. Neutrophil degranulation activation was assessed by enhanced flow cytometry expression of cell surface markers of distinct granule subsets. Chromatography fractions with enhanced neutrophil activation from active versus inactive LN serum were characterized with quantitative LC-MS/MS analysis.
Results
Serum fractions from LN patients in active status stimulated neutrophil degranulation compared with inactive disease samples. Quantitative mass spectrometry analysis identified differences in the serum proteome with potential associations with LN activity and inflammation. Candidates of interest with higher abundance in the active LN serum included LGALS3BP (promotes cell adhesion and is a candidate urinary marker for LN), CD14 (pro-inflammatory cell receptor), ApoC3 (Implicated in cardiovascular risk in SLE), and C5a (neutrophil activator and approved therapeutic target for ANCA-associated vasculitis).
Conclusion
These studies identified serum proteins that potentially play critical roles in LN pathology and that can serve as novel markers of activity and be therapeutically targeted. Since C5a inhibition is an approved treatment for other types of inflammatory kidney injury, our studies will provide support for use in LN and identify candidate LN patients for this treatment.
Funding
- NIDDK Support