DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN
- 1 January 2018
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 29 (1), 231-239
- https://doi.org/10.1681/ASN.2017050566
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.This publication has 32 references indexed in Scilit:
- A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein ResponseCell, 2016
- IgG Subclass Staining in Routine Renal Biopsy MaterialThe American Journal of Surgical Pathology, 2016
- Endoplasmic reticulum‐resident chaperones modulate the inflammatory and angiogenic responses of endothelial cellsBritish Journal of Dermatology, 2015
- Clinical Proteome Informatics Workbench Detects Pathogenic Mutations in Hereditary AmyloidosesJournal of Proteome Research, 2014
- Long-term Kidney Disease Outcomes in Fibrillary Glomerulonephritis: A Case Series of 27 PatientsAmerican Journal of Kidney Diseases, 2013
- Laser Microdissection and Proteomic Analysis of Amyloidosis, Cryoglobulinemic GN, Fibrillary GN, and Immunotactoid GlomerulopathyClinical Journal of the American Society of Nephrology, 2013
- Fibrillary Glomerulonephritis and Immunotactoid GlomerulopathyJournal of the American Society of Nephrology, 2008
- Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic featuresKidney International, 2003
- Ultrastructural immunohistochemical localization of polyclonal IgG, C3, and amyloid P component on the congo red-negative amyloid-like fibrils of fibrillary glomerulopathy.1992
- Fibrillary glomerulonephritis: An entity with unusual immunofluorescence featuresKidney International, 1987