Proliferative glomerulonephritis with monoclonal IgG deposits: A distinct entity mimicking immune-complex glomerulonephritis

Samih H. Nasr, Glen S. Markowitz, M. Barry Stokes, Surya V. Seshan, Elsa Valderrama, Gerald B. Appel, Pierre Aucouturier, Vivette D. D'Agati

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Background. Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. Methods. Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%). Results. The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1κ, one IgG1λ, one IgG2λ, four IgG3κ, and one IgG3λ). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80% (mean serum creatinine 2.8 mg/dL. range 0.9 to 8.0). proteinuria in 100% (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGκ and two IgGλ); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). Conclusion. Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.

Original languageEnglish (US)
Pages (from-to)85-96
Number of pages12
JournalKidney International
Volume65
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Fingerprint

Glomerulonephritis
Antigen-Antibody Complex
Immunoglobulin G
Light
Immunoglobulins
Cryoglobulinemia
Heavy Chain Disease
Tissue Fixation
Staining and Labeling
Membranoproliferative Glomerulonephritis
Kidney
Paraproteinemias
Nephrotic Syndrome
Proteinuria
Renal Insufficiency
Fluorescent Antibody Technique
Blood Proteins
Lymphoma
Creatinine
Electron Microscopy

Keywords

  • Dysproteinemia
  • Glomerulonephritis
  • Monoclonal gammopathy

ASJC Scopus subject areas

  • Nephrology

Cite this

Nasr, S. H., Markowitz, G. S., Stokes, M. B., Seshan, S. V., Valderrama, E., Appel, G. B., ... D'Agati, V. D. (2004). Proliferative glomerulonephritis with monoclonal IgG deposits: A distinct entity mimicking immune-complex glomerulonephritis. Kidney International, 65(1), 85-96. https://doi.org/10.1111/j.1523-1755.2004.00365.x

Proliferative glomerulonephritis with monoclonal IgG deposits : A distinct entity mimicking immune-complex glomerulonephritis. / Nasr, Samih H.; Markowitz, Glen S.; Stokes, M. Barry; Seshan, Surya V.; Valderrama, Elsa; Appel, Gerald B.; Aucouturier, Pierre; D'Agati, Vivette D.

In: Kidney International, Vol. 65, No. 1, 01.2004, p. 85-96.

Research output: Contribution to journalArticle

Nasr, SH, Markowitz, GS, Stokes, MB, Seshan, SV, Valderrama, E, Appel, GB, Aucouturier, P & D'Agati, VD 2004, 'Proliferative glomerulonephritis with monoclonal IgG deposits: A distinct entity mimicking immune-complex glomerulonephritis', Kidney International, vol. 65, no. 1, pp. 85-96. https://doi.org/10.1111/j.1523-1755.2004.00365.x
Nasr, Samih H. ; Markowitz, Glen S. ; Stokes, M. Barry ; Seshan, Surya V. ; Valderrama, Elsa ; Appel, Gerald B. ; Aucouturier, Pierre ; D'Agati, Vivette D. / Proliferative glomerulonephritis with monoclonal IgG deposits : A distinct entity mimicking immune-complex glomerulonephritis. In: Kidney International. 2004 ; Vol. 65, No. 1. pp. 85-96.
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abstract = "Background. Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. Methods. Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21{\%}). Results. The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1κ, one IgG1λ, one IgG2λ, four IgG3κ, and one IgG3λ). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90{\%} of cases, and 40{\%} of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80{\%} (mean serum creatinine 2.8 mg/dL. range 0.9 to 8.0). proteinuria in 100{\%} (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44{\%}, and microhematuria in 60{\%}. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50{\%} of cases (including three IgGκ and two IgGλ); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). Conclusion. Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.",
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AU - Stokes, M. Barry

AU - Seshan, Surya V.

AU - Valderrama, Elsa

AU - Appel, Gerald B.

AU - Aucouturier, Pierre

AU - D'Agati, Vivette D.

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N2 - Background. Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. Methods. Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%). Results. The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1κ, one IgG1λ, one IgG2λ, four IgG3κ, and one IgG3λ). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80% (mean serum creatinine 2.8 mg/dL. range 0.9 to 8.0). proteinuria in 100% (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGκ and two IgGλ); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). Conclusion. Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.

AB - Background. Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. Methods. Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%). Results. The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1κ, one IgG1λ, one IgG2λ, four IgG3κ, and one IgG3λ). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80% (mean serum creatinine 2.8 mg/dL. range 0.9 to 8.0). proteinuria in 100% (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGκ and two IgGλ); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). Conclusion. Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.

KW - Dysproteinemia

KW - Glomerulonephritis

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