DnaJ homolog subfamily B member 9 is a putative autoantigen in fibrillary GN

Nicole Andeen, Han Yin Yang, Dao Fu Dai, Michael J. MacCoss, Kelly D. Smith

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalJournal of the American Society of Nephrology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Autoantigens
Proteome
Complement System Proteins
Immunoglobulin G
Laser Capture Microdissection
Tandem Mass Spectrometry
Liquid Chromatography
Paraffin
Formaldehyde
Fluorescent Antibody Technique
Mass Spectrometry
Immunohistochemistry
Staining and Labeling
Kidney
Biopsy
Antibodies
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

DnaJ homolog subfamily B member 9 is a putative autoantigen in fibrillary GN. / Andeen, Nicole; Yang, Han Yin; Dai, Dao Fu; MacCoss, Michael J.; Smith, Kelly D.

In: Journal of the American Society of Nephrology, Vol. 29, No. 1, 01.01.2018, p. 231-239.

Research output: Contribution to journalArticle

Andeen, Nicole ; Yang, Han Yin ; Dai, Dao Fu ; MacCoss, Michael J. ; Smith, Kelly D. / DnaJ homolog subfamily B member 9 is a putative autoantigen in fibrillary GN. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 1. pp. 231-239.
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