ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-OR092

Proliferative Glomerulonephritis with Monoclonal Light Chain Deposits

Session Information

Category: Pathology and Lab Medicine

  • 1602 Pathology and Lab Medicine: Clinical

Authors

  • Nasr, Samih H., Mayo Clinic, Rochester, Minnesota, United States
  • Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
  • Sirac, Christophe, CNRS, Limoges, France
  • Theis, Jason David, Mayo Clinic, Rochester, Minnesota, United States
  • Hogan, Jonathan J., Hospital of the University of Pennsylvania, Haddonfield, New Jersey, United States
  • Said, Samar M., Mayo Clinic, Rochester, Minnesota, United States
  • Dasari, Surendra, Mayo Clinic, Rochester, Minnesota, United States
  • Vrana, Julie A., Mayo Clinic, Rochester, Minnesota, United States
  • Mcphail, Ellen Darcy, Mayo Clinic, Rochester, Minnesota, United States
  • Cornell, Lynn D., Mayo Clinic, Rochester, Minnesota, United States
  • D'Agati, Vivette D., Columbia University College of Physicians and Surgeons, New York, New York, United States
  • Leung, Nelson, Mayo Clinic, Rochester, Minnesota, United States
  • Bridoux, Frank, Hôpital Jean Bernard, CHU Poitiers, Poitiers, France
Background

Most cases of proliferative glomerulonephritis with monoclonal immunoglobulin (MIg) deposits (PGNMID) are of the IgG isotype (particularly IgG3).

Methods

We describe the first clinicopathologic and proteomic series of PGNMID with MIg light chain (LC) deposits (PGNMID-LC).

Results

This multicenter cohort consisted of 18 patients (median age 60 years, 72% male) who presented with nephritic or nephrotic syndrome. The underlying hematologic condition was MGRS (72%) or multiple myeloma (28%). MIg was identified by serum and urine immunofixation in 61% and 69% of patients, abnormal serum FLC in 77%, and corresponding nephritogenic plasma cell clone in the bone marrow in 88%. Renal biopsy showed MPGN in most patients; glomerular deposition of MIg LC (κ in 67% and λ in 33%) and C3 (100%), without extraglomerular deposits, IgG, IgA, or C1q deposits, by immunofluorescence (IF); and subendothelial (100%), mesangial (100%) and subepithelial (72%) granular electron dense deposits by electron microscopy. Paraffin IF done in 39% of cases showed similar results to IF on frozen tissue. Laser microdissection/mass spectrometry performed on 4 cases of κ PGNMID-LC revealed spectra for Ig κ constant and variable domains and complement alternative pathway (CAP) and terminal complex proteins (particularly C3 and C9) in 3 without spectra for Ig γ, α, μ, λ, or classical complement pathway proteins. In contrast, 6 cases of κ LCDD analyzed did not show spectra for complement proteins. Complement functional assays in 1 patient revealed that a serum fraction enriched with the monoclonal Vl3 LC induced CAP activation in normal human serum. Follow up (median 66 months) was available in 16 patients. Renal response occurred in 6 of 10 patients treated with plasma cell-directed chemotherapy but not in 6 who did not. Hematologic response was evaluable in 8. All 6 with hematologic complete response achieved renal response while the 2 with hematologic partial or no response did not.

Conclusion

PGNMID-LC is a variant of PGNMID with higher detection rate of the nephritogenic plasma cell clone. Proper recognition is crucial as plasma cell clone-directly therapy appears to improve renal prognosis. Activation of CAP by MIg LC likely plays a central role in its pathogenesis.