Abstract: SA-PO0923
A Deletion-Driven Complement Activation Conglomeration in IgA-Dominant Infection-Related Glomerulonephritis?
Session Information
- Glomerular Case Reports: ANCA, IgA, IgG, and More
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Nguyen, Julia, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Malone, Laura, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Joshi, Megha Raj, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Watson, Maura A., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Introduction
IgA-dominant infection-related glomerulonephritis (IRGN) results from glomerular immune complex deposition (ICD) typically triggered by Staphylococcal (Staph) or Streptococcal infections. Eradicating the infection helps prevent further ICD. Risk factors include older age, diabetes, and prior Staph infections. Patients usually present with hematuria, proteinuria, renal injury and poor prognosis (<20% fully recover). We report a case of IRGN without infection history in a male with CFHR1 and CFHR3 heterozygous deletions which - despite unclear clinical significance - may point to a regulatory role in complement activation and ICD.
Case Description
A 25-year-old male presented with hypertensive emergency, mixed nephritic/nephrotic syndrome and acute kidney failure. Serologic work-up was notable for borderline positive antistreptolysin O titer and mildly low serum complement (C3 88 mg/dl). Negative tests included C3 nephritic factor, ANCA panel, GBM Ab, and additional autoimmune and infectious work-up. Renal biopsy revealed a crescentic glomerulonephritis (GN) with diffuse mesangial and membranoproliferative type pattern. Immunofluorescence showed strong C3 (3+) and IgA (2+) staining, with characteristic subepithelial hump-like deposits on electron microscopy and few subendothelial deposits. These features favored a diagnosis of IgA dominant IRGN over IgA nephropathy, IgA vasculitis, or C3 GN. Genetics testing was negative for inherited kidney disease panel, CM-TMA/aHUS, C3G, CFH-H3, and C5. Interestingly, heterozygous deletions for CFHR1 and CFHR3 gene clusters were detected.
Discussion
Exact mechanisms of IgA-dominant IRGN are poorly understood but infection mediated triggers are theorized, with circulating antigen-antibody glomerular ICD. Complete mechanisms responsible for complement mediated ICD activation have yet to be fully elucidated. CFHR1 and CFHR3 have been implicated in regulatory roles in C3b processing and increased risk of atypical hemolytic uremic syndrome. This case raises questions regarding their role in predisposition for IRGN as well.
The views expressed in this abstract are those of the author(s) and do not necessarily reflect the official policy of the Department of Defense or the United States Government.