Kidney Week

Abstract: SA-PO0632

Limited Diagnostic Utility of Light Chain and IgA Subclass Staining in IgA-Type Monoclonal Gammopathy of Renal Significance

Session Information

• Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
  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

• Manabe, Shun, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Shun Manabe, MD, PhD

• Nakai, Anna, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Anna Nakai, MD

• Seki, Momoko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Momoko Seki

• Ushio, Yusuke, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Yusuke Ushio, MD, PhD

• Takahashi, Rina, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Rina Takahashi, MD, PhD

• Kobayashi, Shizuka, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Shizuka Kobayashi, MD

• Makabe, Shiho, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Shiho Makabe, MD

• Ito, Naoko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Naoko Ito, MD

• Taneda, Sekiko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Sekiko Taneda, MD, PhD

• Ito, Jun, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Jun Ito, MD, PhD

• Kataoka, Hiroshi, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Hiroshi Kataoka, MEd

• Hoshino, Junichi, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Junichi Hoshino, MD, PhD, MPH

Background

Monoclonal gammopathy of renal significance (MGRS) causes renal injury via monoclonal immunoglobulin deposits. Unlike IgG-MGRS, diagnosing IgA-MGRS is challenging due to having only two IgA subclasses. Primary IgA nephropathy (IgAN) consistently shows IgA1 and frequent λ-light chain dominance, mimicking IgA-MGRS. We evaluated light chain and IgA subclass staining utility in IgA-dominant glomerular diseases.

Methods

We reviewed native kidney biopsies with IgA-dominant deposition at our institution (Jan 2015–Aug 2024). We assessed κ/λ restriction, IgA subclass, pathology, serum M-protein, and outcomes.

Results

Of 326 cases, diagnoses were IgAN (n=302), IgA vasculitis (n=19), and others (n=5: 1 IgA2-MIDD, 2 suspected IgA1-PGNMID, 1 MGA, 1 nodular glomerulosclerosis). In Figure 1, light chain restriction (intensity difference [Δ]≥1.0) occurred in 50 patients (15.3%; 14κ, 36λ), and Δ≥1.5 in 26 (8.0%). Of 48 cases with Δ≥1.0 and subclass imbalance, diagnoses were IgAN (45), IgA vasculitis (1), and suspected IgA1-PGNMID (2). The rare IgA2-MIDD case lacked significant light chain restriction. All 23 cases with follow-up lacked serum M-protein. Of two suspected IgA1-PGNMID cases, one achieved partial remission with steroid pulses and cyclosporine; the other was refractory but confirmed as IgA1-PGNMID via repeat biopsy.

Conclusion

Light chain restriction in IgA deposits often reflects polyclonal IgAN's intrinsic λ-dominance, not true MGRS. Conversely, true monoclonal diseases (e.g., IgA2-MIDD) may lack κ/λ restriction due to non-specific deposition. Thus, immunofluorescence alone cannot diagnose IgA-MGRS. Since PGNMID frequently presents without serum M-protein, its absence cannot exclude the diagnosis. A comprehensive approach integrating pathology, M-protein screening, clinical findings, and treatment response is essential to identify IgA-MGRS.