DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis

Samih H. Nasr, Julie A. Vrana, Surendra Dasari, Frank Bridoux, Mary E. Fidler, Sihem Kaaki, Nathalie Quellard, Alexia Rinsant, Jean Michel Goujon, Sanjeev M Sethi, Fernando Custodio Fervenza, Lynn D. Cornell, Samar M. Said, Ellen McPhail, Loren P. Herrera Hernandez, Joseph Peter Grande, Marie C Hogan, John C Lieske, Nelson Leung, Paul J. Kurtin & 1 others Mariam P Alexander

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: Fibrillary glomerulonephritis (FGN) is a rare disease with unknown pathogenesis and a poor prognosis. Until now, the diagnosis of this disease has required demonstration of glomerular deposition of randomly oriented fibrils by electron microscopy that are Congo red negative and stain with antisera to Igs. We recently discovered a novel proteomic tissue biomarker for FGN, namely, DNAJB9. Methods: In this work, we developed DNAJB9 immunohistochemistry and tested its sensitivity and specificity for the diagnosis of FGN. This testing was performed on renal biopsy samples from patients with FGN (n = 84), amyloidosis (n = 21), a wide variety of non-FGN glomerular diseases (n = 98), and healthy subjects (n = 11). We also performed immunoelectron microscopy to determine whether DNAJB9 is localized to FGN fibrils. Results: Strong, homogeneous, smudgy DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN. The 2 cases that did not stain for DNAJB9 were unique, as they had glomerular staining for IgG only (without κ or λ) on immunofluorescence. DNAJB9 staining was not observed in cases of amyloidosis, in healthy subjects, or in non-FGN glomerular diseases (with the exception of very focal staining in 1 case of smoking-related glomerulopathy), indicating 98% sensitivity and > 99% specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules. Conclusion: DNAJB9 immunohistochemistry is sensitive and specific for FGN. Incorporation of this novel immunohistochemical biomarker into clinical practice will now allow more rapid and accurate diagnosis of this disease.

Original languageEnglish (US)
Pages (from-to)56-64
Number of pages9
JournalKidney International Reports
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2018

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Glomerulonephritis
Staining and Labeling
Immunoelectron Microscopy
Amyloidosis
Healthy Volunteers
Coloring Agents
Biomarkers
Immunohistochemistry
Congo Red
Rare Diseases
Amyloid
Microtubules
Proteomics
Fluorescent Antibody Technique
Immune Sera
Electron Microscopy
Immunoglobulin G
Smoking
Kidney
Biopsy

Keywords

  • biomarker
  • DNAJB9
  • fibrillary glomerulonephritis
  • immunoelectron microscopy
  • immunohistochemistry
  • kidney biopsy

ASJC Scopus subject areas

  • Nephrology

Cite this

DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. / Nasr, Samih H.; Vrana, Julie A.; Dasari, Surendra; Bridoux, Frank; Fidler, Mary E.; Kaaki, Sihem; Quellard, Nathalie; Rinsant, Alexia; Goujon, Jean Michel; Sethi, Sanjeev M; Fervenza, Fernando Custodio; Cornell, Lynn D.; Said, Samar M.; McPhail, Ellen; Herrera Hernandez, Loren P.; Grande, Joseph Peter; Hogan, Marie C; Lieske, John C; Leung, Nelson; Kurtin, Paul J.; Alexander, Mariam P.

In: Kidney International Reports, Vol. 3, No. 1, 01.01.2018, p. 56-64.

Research output: Contribution to journalArticle

Nasr, SH, Vrana, JA, Dasari, S, Bridoux, F, Fidler, ME, Kaaki, S, Quellard, N, Rinsant, A, Goujon, JM, Sethi, SM, Fervenza, FC, Cornell, LD, Said, SM, McPhail, E, Herrera Hernandez, LP, Grande, JP, Hogan, MC, Lieske, JC, Leung, N, Kurtin, PJ & Alexander, MP 2018, 'DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis', Kidney International Reports, vol. 3, no. 1, pp. 56-64. https://doi.org/10.1016/j.ekir.2017.07.017
Nasr, Samih H. ; Vrana, Julie A. ; Dasari, Surendra ; Bridoux, Frank ; Fidler, Mary E. ; Kaaki, Sihem ; Quellard, Nathalie ; Rinsant, Alexia ; Goujon, Jean Michel ; Sethi, Sanjeev M ; Fervenza, Fernando Custodio ; Cornell, Lynn D. ; Said, Samar M. ; McPhail, Ellen ; Herrera Hernandez, Loren P. ; Grande, Joseph Peter ; Hogan, Marie C ; Lieske, John C ; Leung, Nelson ; Kurtin, Paul J. ; Alexander, Mariam P. / DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. In: Kidney International Reports. 2018 ; Vol. 3, No. 1. pp. 56-64.
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T1 - DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis

AU - Nasr, Samih H.

AU - Vrana, Julie A.

AU - Dasari, Surendra

AU - Bridoux, Frank

AU - Fidler, Mary E.

AU - Kaaki, Sihem

AU - Quellard, Nathalie

AU - Rinsant, Alexia

AU - Goujon, Jean Michel

AU - Sethi, Sanjeev M

AU - Fervenza, Fernando Custodio

AU - Cornell, Lynn D.

AU - Said, Samar M.

AU - McPhail, Ellen

AU - Herrera Hernandez, Loren P.

AU - Grande, Joseph Peter

AU - Hogan, Marie C

AU - Lieske, John C

AU - Leung, Nelson

AU - Kurtin, Paul J.

AU - Alexander, Mariam P

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Fibrillary glomerulonephritis (FGN) is a rare disease with unknown pathogenesis and a poor prognosis. Until now, the diagnosis of this disease has required demonstration of glomerular deposition of randomly oriented fibrils by electron microscopy that are Congo red negative and stain with antisera to Igs. We recently discovered a novel proteomic tissue biomarker for FGN, namely, DNAJB9. Methods: In this work, we developed DNAJB9 immunohistochemistry and tested its sensitivity and specificity for the diagnosis of FGN. This testing was performed on renal biopsy samples from patients with FGN (n = 84), amyloidosis (n = 21), a wide variety of non-FGN glomerular diseases (n = 98), and healthy subjects (n = 11). We also performed immunoelectron microscopy to determine whether DNAJB9 is localized to FGN fibrils. Results: Strong, homogeneous, smudgy DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN. The 2 cases that did not stain for DNAJB9 were unique, as they had glomerular staining for IgG only (without κ or λ) on immunofluorescence. DNAJB9 staining was not observed in cases of amyloidosis, in healthy subjects, or in non-FGN glomerular diseases (with the exception of very focal staining in 1 case of smoking-related glomerulopathy), indicating 98% sensitivity and > 99% specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules. Conclusion: DNAJB9 immunohistochemistry is sensitive and specific for FGN. Incorporation of this novel immunohistochemical biomarker into clinical practice will now allow more rapid and accurate diagnosis of this disease.

AB - Introduction: Fibrillary glomerulonephritis (FGN) is a rare disease with unknown pathogenesis and a poor prognosis. Until now, the diagnosis of this disease has required demonstration of glomerular deposition of randomly oriented fibrils by electron microscopy that are Congo red negative and stain with antisera to Igs. We recently discovered a novel proteomic tissue biomarker for FGN, namely, DNAJB9. Methods: In this work, we developed DNAJB9 immunohistochemistry and tested its sensitivity and specificity for the diagnosis of FGN. This testing was performed on renal biopsy samples from patients with FGN (n = 84), amyloidosis (n = 21), a wide variety of non-FGN glomerular diseases (n = 98), and healthy subjects (n = 11). We also performed immunoelectron microscopy to determine whether DNAJB9 is localized to FGN fibrils. Results: Strong, homogeneous, smudgy DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN. The 2 cases that did not stain for DNAJB9 were unique, as they had glomerular staining for IgG only (without κ or λ) on immunofluorescence. DNAJB9 staining was not observed in cases of amyloidosis, in healthy subjects, or in non-FGN glomerular diseases (with the exception of very focal staining in 1 case of smoking-related glomerulopathy), indicating 98% sensitivity and > 99% specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules. Conclusion: DNAJB9 immunohistochemistry is sensitive and specific for FGN. Incorporation of this novel immunohistochemical biomarker into clinical practice will now allow more rapid and accurate diagnosis of this disease.

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