Abstract: SA-PO1241
Large Single-Center Clinicopathologic Experience of Monotypic Membranous Nephropathy with Cryptic Drivers
Session Information
- Onconephrology: Epidemiological Trends, Risk Stratification, and Clinical Outcomes
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Hirschi, Zoe Alaniz, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Hu, Alvin, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Anumolu, Rajesh, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Hofmann, Patrick, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Chowdhury, Raad Bin Zakir, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Shah, Sujal I., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background
Monotypic membranous nephropathy (MN) is a rare pattern of MN characterized by subepithelial immune deposits with light chain or IgG subclass restriction. Some cases occur in the context of plasma cell or B-cell lymphoproliferative disorders (LPD), though many drivers remain uncertain. Given the ill-defined clinical presentation, questions remain about optimal management.
Methods
A single-center, retrospective analysis of 14 patients diagnosed with monotypic MN, evaluating clinicopathologic patterns and treatment outcomes based on underlying drivers. Demographics, clinical data, pathology, and post-intervention follow-up were reviewed.
Results
The median age was 54 years, with a 1:1 sex ratio. All patients presented with proteinuria (57.1% nephrotic range). Patients were categorized by underlying disease driver into B-cell LPD (n = 4), plasma-cell LPD (n = 2), autoimmune (n = 3), and unidentified (n = 5), and were grouped into LPD (n = 6; 42.9%) and non-LPD (n = 8; 57.1%) cohorts for comparative analysis. Two patients, both with plasma-cell LPD, had detectable monoclonal Ig. IgG2 restriction was 100% specific for B-cell LPD, while IgG1 restriction dominated all other subgroups. Kappa restriction was seen in 78.6% of the total cohort. PLA2R staining was negative in all cases tested. Ultrastructural organized deposits (microtubular, fibrillar) were more prevalent in the non-LPD cohort than in the LPD cohort (37.5% vs 16.7%). Treatment diverged by driver: non-LPD patients predominantly received plasma cell-directed therapy, while LPD therapy was clone-directed. By 12 months, the LPD cohort had higher rates of complete remission (50% vs 12.5%), with the non-LPD cohort achieving predominantly partial remission (62.5%).
Conclusion
This analysis highlights the role of histopathology, specifically IgG subclass staining and deposit morphology, in managing monotypic MN. IgG2 restriction correlated with B-cell LPDs and responded to B-cell-targeted therapies, whereas organized glomerular deposit patterns favored a plasma cell-directed approach. While highest rates of complete remission were achieved by targeting identifiable clones, therapies based on these patterns enabled disease control and reduced proteinuria even in clone-negative patients. These findings suggest that monotypic MN is a distinct clinical entity in which immunophenotypically-guided therapy is essential to optimize outcomes.