Abstract: TH-PO0698
Loss of Decay-Accelerating Factor in Neutrophils Attenuates Proteinuria in a Murine Model of FSGS
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 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
- Bigatti, Carolina, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Cocchini, Lorenzo, IRCCS Ospedale San Raffaele, Milan, Lombardy, Italy
- Korogodsky, Dana, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Angeletti, Andrea, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background
Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome, but its pathophysiology is still unclear. Complement activation has been implicated in disease progression, but the involvement of immune cells, especially neutrophils, has not been clearly defined. Decay-accelerating factor (DAF, also known as CD55) is a complement regulatory protein expressed on neutrophils that may influence their survival and effector function. To test the role of DAF and complement activation in neutrophils in FSGS pathophysiology, we developed mice with conditional deletion or overexpression of DAF in neutrophils
Methods
Male DAFΔS100A8, DAFTgS100A8, and DAFfl/fl mice (aged 8-12 week) received a single retroorbital injection of adriamycin (21 mg/kg). Urinary albumin-to-creatinine ratio (A/C) was measured for 5 weeks. Statistical analysis was performed using a two-way ANOVA.
Results
DAFΔS100A8 developed significantly lower proteinuria compared to DAFfl/fl mice at day 21 and 35 (p=0.038 and p=0.0011, respectively). To further confirm the possible role of neutrophils DAF in glomerular injury, we analyzed transgenic mice overexpressing DAF in neutrophils (DAFTgS100A8), which showed a marked increase in A/C at day 7, 21, 35 (figure 1). Flow cytometry revealed no difference in the percentage of renal CD45+CD11b+Ly6G+ neutrophils among groups across multiple timepoints (day 0, 1, 3, 5, 14, 35).
Conclusion
These findings suggest that DAF expression on neutrophils promotes glomerular injury in adriamycin-induced FSGS. Loss of neutrophil DAF protects against proteinuria, possibly by limiting effector functions such as Neutrophils Extracellular Traps (NET) release or Radical Oxygen species (ROS) production. Neutrophil-specific modulation of complement regulatory pathways may represent a novel therapeutic target in FSGS.