Abstract: TH-PO0437
Factor H Autoantibodies and Low C3 in Plasma Cell-Rich Tubulointerstitial Nephritis: A Potential Link to IgG4-Spectrum Kidney Disease
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Aladham, Ahmed, University of Illinois Chicago, Chicago, Illinois, United States
- Levine, Jerrold S., University of Illinois Chicago, Chicago, Illinois, United States
Introduction
IgG4-related kidney disease (IgG4-RKD) is a fibroinflammatory disorder characterized by plasma cell-rich tubulointerstitial nephritis (TIN), storiform fibrosis, and IgG4-positive plasma cell infiltration. Factor H autoantibodies (FHAAs) can lead to complement-mediated kidney diseases, and IgG4 FHAAs have been described in IgG4-RKD with complement-mediated TMA. We present a case of plasma cell-rich TIN with positive FHAAs and low C3, suggesting complement dysregulation in IgG4-spectrum disease.
Case Description
A 70-year-old man with HIV, treated HCV, and prostate cancer s/p prostatectomy presented with rapid CKD progression (creatinine 1.24→4.68 mg/dL over 6 months, stabilizing ~6.0). Heavy proteinuria (15.33 g, predominantly non-albumin) decreased to ~1 g. Serum IgG4 was normal; ANCA, cryoglobulins, PLA2R, and SPEP were negative. Serial complements declined (C3 83, C4 29). Biopsy revealed dense plasma cell-rich interstitial inflammation and marked fibrosis. IgG4 immunostaining showed focal positivity (~15%, up to 18/HPF). Storiform fibrosis, phlebitis, and immune-complex deposits were absent. University of Iowa Complement Biomarker Panel revealed positive FHAAs, deemed of clinical significance.
Discussion
Borderline IgG4 positivity raises suspicion for IgG4-RKD despite not meeting classic criteria. HIV and chronic urologic instrumentation can drive plasma cell-rich TIN. However, positive FHAAs, eosinophilia (1000 cells/µL), and IgG4-positive plasma cell proportion suggest immune dysregulation, consistent with reports of anti-Factor H IgG4 autoantibodies driving complement activation in IgG4-RKD. Low C3 further supports this. FHAA subclass characterization in similar cases may expand understanding of IgG4-RKD pathogenesis and inform complement-directed therapy.