DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN

Nicole K Andeen; Han-Yin Yang; Dao-Fu Dai; Michael J MacCoss; Kelly D Smith

doi:10.1681/ASN.2017050566

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DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN

Journal article

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DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN

Nicole K Andeen, Han-Yin Yang, Dao-Fu Dai, Michael J MacCoss and Kelly D Smith

Journal of the American Society of Nephrology, Vol.29(1), pp.231-239

01/2018

DOI: 10.1681/ASN.2017050566

PMCID: PMC5748922

PMID: 29097624

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Abstract

Fibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12-24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. These studies identified DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein detected only in fibrillary GN cases. The glomerular proteome of fibrillary GN cases also contained IgG1 as the dominant Ig and proteins of the classic complement pathway. In fibrillary GN specimens only, immunofluorescence and immunohistochemistry with an anti-DNAJB9 antibody showed strong and specific staining of the glomerular tufts in a distribution that mimicked that of the immune deposits. Our results identify DNAJB9 as a putative autoantigen in fibrillary GN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease.

HSP40 Heat-Shock Proteins - metabolism

Autoantigens - metabolism

Molecular Chaperones - metabolism

Humans

Glomerulonephritis - immunology

Membrane Proteins - immunology

Glomerulonephritis - metabolism

Complement System Proteins - metabolism

Tandem Mass Spectrometry

Autoantigens - immunology

Fluorescent Antibody Technique

HSP40 Heat-Shock Proteins - immunology

Chromatography, Liquid

Kidney Glomerulus - metabolism

Membrane Proteins - metabolism

Molecular Chaperones - immunology

Proteome - metabolism

Immunoglobulin G - metabolism

Details

Title: Subtitle: DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN
Creators: Nicole K Andeen - Departments of Pathology and
Han-Yin Yang - Genome Sciences, University of Washington, Seattle, Washington
Dao-Fu Dai - Departments of Pathology and
Michael J MacCoss - Genome Sciences, University of Washington, Seattle, Washington
Kelly D Smith - Departments of Pathology and kelsmith@uw.edu
Resource Type: Journal article
Publication Details: Journal of the American Society of Nephrology, Vol.29(1), pp.231-239
Publisher: United States
DOI: 10.1681/ASN.2017050566
PMID: 29097624
PMCID: PMC5748922
ISSN: 1046-6673
eISSN: 1533-3450
Grant note: R21 CA192983 / NCI NIH HHS P41 GM103533 / NIGMS NIH HHS P01 AG001751 / NIA NIH HHS P30 AG013280 / NIA NIH HHS
Language: English
Date published: 01/2018
Academic Unit: Pathology; Iowa Neuroscience Institute; Radiation Oncology
Record Identifier: 9984070450602771

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