Abstract: SA-PO0719
A Case of Terminal Complement Pathway Dysregulation in C3 Glomerulonephritis
Session Information
- Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
October 24, 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
- Kroll, Danielle, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Rodriguez Gomez, Gloria Paulina, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Hirpara, Samir, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Henderson, Joel M., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Sula Karreci, Esilida, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Introduction
C3 glomerulonephritis (C3GN) is a rare complement-mediated glomerular disease caused by dysregulation of the alternative complement pathway. Nephritic factors (NeF), which are autoantibodies against complement convertases, are frequent causes of C3GN. While C3 NeF has been classically associated with C3GN, C5 NeF is rarely seen in C3GN in isolation. In these cases, C5 NeF stabilizes C5 convertase, leading to excessive consumption of C3 and C5 and production of sC5b-9. Studies have shown that elevated sC5b-9 predicts response to immunosuppression, but this has not been studied in a patient with isolated C5 NeF. Here, we present the management of isolated C5 NeF-driven C3GN.
Case Description
An 18-year-old patient was evaluated in the emergency department for new nephrotic syndrome after hypoalbuminemia and hyperlipidemia were discovered on routine labs. Renal biopsy revealed C3GN with membranoproliferative pattern of injury. Further immunologic investigation was notable for abolished alternative pathway, positive fluid-phase activity, negative C3 NeF and 1+ C5 NeF, with reduced C3, C4, C5, and properdin and elevated sC5b-9. Genetic testing was noncontributory.
Discussion
The patient was started on mycophenolate mofetil and prednisone once pathology was confirmed. Losartan and empagliflozin were also used adjunctively for proteinuria. Despite their complement profile suggesting a positive response to immunosuppression, their proteinuria worsened after one month of management and subsequent dose escalation. Eculizumab, a C5 convertase inhibitor, works by preventing the activation of the terminal complement pathway. Though the biochemistry underlying C5 NeF driven C3GN would portend a positive treatment response to eculizumab, this remains to be seen. Treatment with eculizumab was recently initiated at the time of submission, and monitoring remains ongoing.
Electron microscopy demonstrating mesangial and subendothelial deposits.