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Protein Mass Spectrometry Made Simple
- Source :
- Journal of the American Society of Nephrology : JASN. 29(6)
- Publication Year :
- 2018
-
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.
- Subjects :
- Protein mass spectrometry
Chemistry
030232 urology & nephrology
Autoantibody
Proteins
General Medicine
Computational biology
Mass spectrometry
Proteomics
Autoantigens
Mass Spectrometry
03 medical and health sciences
0302 clinical medicine
Nephrology
Clinical Research
030212 general & internal medicine
Subjects
Details
- ISSN :
- 15333450
- Volume :
- 29
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Accession number :
- edsair.doi.dedup.....ddfae1863c5080c19edbd886fc20b0be