DnaJ heat shock protein family B member 9 is a novel biomarker for fibrillary GN

Surendra Dasari, Mariam P Alexander, Julie A. Vrana, Jason D. Theis, John R. Mills, Vivian Negron, Sanjeev M Sethi, Angela Dispenzieri, W Edward Jr. Highsmith, Samih H. Nasr, Paul J. Kurtin

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Abstract

Fibrillary GN (FGN) is a rare primary glomerular disease. Histologic and histochemical features of FGN overlap with those of other glomerular diseases, and no unique histologic biomarkers for diagnosing FGN have been identified. We analyzed the proteomic content of glomeruli in patient biopsy specimens and detected DnaJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. Compared with amyloidosis glomeruli, FGN glomeruli exhibited a .6-fold overexpression of DNAJB9 protein. Sanger sequencing and protein sequence coverage maps showed that the DNAJB9 protein deposited in FGN glomeruli did not have any major sequence or structural alterations. Notably, we detected DNAJB9 in all patients with FGN but not in healthy glomeruli or in 19 types of non-FGN glomerular diseases. We also observed the codeposition of DNAJB9 and Ig-g. Overall, these findings indicate that DNAJB9 is an FGN marker with 100% sensitivity and 100% specificity. The magnitude and specificity of DNAJB9 overabundance in FGN also suggests that this protein has a role in FGN pathogenesis. With this evidence, we propose that DNAJB9 is a strong biomarker for rapid diagnosis of FGN in renal biopsy specimens.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalJournal of the American Society of Nephrology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2018

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HSP40 Heat-Shock Proteins
Heat-Shock Proteins
Biomarkers
Proteins
Biopsy
Protein Sequence Analysis
Amyloidosis
Proteomics
Kidney
Sensitivity and Specificity
IgA receptor

ASJC Scopus subject areas

  • Nephrology

Cite this

DnaJ heat shock protein family B member 9 is a novel biomarker for fibrillary GN. / Dasari, Surendra; Alexander, Mariam P; Vrana, Julie A.; Theis, Jason D.; Mills, John R.; Negron, Vivian; Sethi, Sanjeev M; Dispenzieri, Angela; Highsmith, W Edward Jr.; Nasr, Samih H.; Kurtin, Paul J.

In: Journal of the American Society of Nephrology, Vol. 29, No. 1, 01.01.2018, p. 51-56.

Research output: Contribution to journalArticle

Dasari, Surendra ; Alexander, Mariam P ; Vrana, Julie A. ; Theis, Jason D. ; Mills, John R. ; Negron, Vivian ; Sethi, Sanjeev M ; Dispenzieri, Angela ; Highsmith, W Edward Jr. ; Nasr, Samih H. ; Kurtin, Paul J. / DnaJ heat shock protein family B member 9 is a novel biomarker for fibrillary GN. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 1. pp. 51-56.
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