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Abstract: PO1890

Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: Searching for the Underlying Clone

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Javaugue, Vincent, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
  • Pascal, Virginie, Centre Hospitalier Universitaire de Limoges, Limoges, France
  • Bender, Sébastien, Centre National de la Recherche Scientifique, Limoges, France
  • Goujon, Jean-Michel, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
  • Touchard, Guy, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
  • Sirac, Christophe, Centre National de la Recherche Scientifique, Limoges, France
  • Bridoux, Frank, Centre Hospitalier Universitaire de Poitiers, Poitiers, France

Group or Team Name

  • Centre national de référence amylose AL et autres maladies par dépôts d'Ig monoclonales
Background

The pathophysiological mechanisms of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) are still largely unknown. Only 30% of PGNMID cases have a detectable circulating monoclonal immunoglobulin (Ig) and a bone marrow corresponding clone.

Methods

We reviewed a French cohort of PGNMID with particular focus on hematological characteristics. A high-throughput sequencing assay from bone marrow and/or blood mRNA encoding immunoglobulins (RACE-RepSeq) was used to detect the underlying clone.

Results

Seventy-one patients (M/F ratio=1.6, median age 59 years) were included. At diagnosis, 73% had renal insufficiency (median serum creatinine=1.7 mg/dL). All patients had proteinuria, with nephrotic syndrome in 59% and microscopic hematuria in 85% of cases. No patient had extra-renal manifestations. By light microscopy, kidney biopsy revealed membranoproliferative glomerulonephritis (74%), mesangial glomerulonephritis (14%) or membranous glomerulonephritis (12%). By immunofluorescence (IF), deposits stained for IgG in 55 cases (mostly IgG3κ), IgM in 7 cases, IgA in 4 cases or light chain (LC) only in 5 cases. Serum and/or urine immunofixation was positive in 26 cases (37%). An underlying clone was found in 21 cases (30%) using bone marrow or blood flow cytometry analysis. The clonal detection rate was particularly low in IgG3κ-PGNMID (9%). The nature of the clone differed with PGNMID subtype: lymphoplasmacytic in IgM-PGNMID, and plasmacytic in IgA/LC-PGNMID. RACE-RepSeq analysis failed to detect a bone marrow or blood clone in 18/26 cases (IgG3κ-PGNMID, n=17; IgGAκ-PGNMID, n=1). IF analysis of kidney samples using anti-Vκ antibodies showed positive staining for Vκ1, Vκ2, Vκ3 and Vκ4 in 3/3 tested IgG3k-PGNMID patients without a detectable clone, whereas deposits stained only for Vκ2 in one IgG1k-PGNMID patient who had a bone marrow Vκ2 clone by RACE-RepSeq analysis.

Conclusion

These results suggest that PGNMID is a heterogeneous medical condition and that some cases might involve oligoclonal production of nephrotoxic Ig restricted to the IgG3k isotype. Such cases should no longer be classified as MGRS.