Abstract: TH-OR021

DNAJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary Glomerulonephritis

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Andeen, Nicole K., University of Washington, Seattle, Washington, United States
  • Yang, Han-Yin, University of Washington, Seattle, Washington, United States
  • Dai, Dao-Fu, University of Washington, Seattle, Washington, United States
  • Maccoss, Michael, University of Washington, Seattle, Washington, United States
  • Smith, Kelly D., University of Washington, Seattle, Washington, United States
Background

Fibrillary glomerulonephritis (FGN) is a rare form of glomerulonephritis of uncertain pathogenesis, which is characterized by the glomerular accumulations of non-branching, randomly arranged fibrils composed of immunoglobulin and complement proteins. In this study, we utilized mass spectrometry to comprehensively define the glomerular proteome in FGN compared to controls and non-FGN renal diseases.

Methods

Glomeruli from formalin-fixed and paraffin-embedded biopsies were isolated using laser capture microdissection (LCM) and analyzed with liquid chromatography and data-dependent tandem mass spectrometry (LC MS/MS). Findings were correlated with immunohistochemistry (IHC).

Results

These studies identified DNAJ homolog subfamily B member 9 (DNAJB9) as a frequently sampled protein by mass spectrometry in FGN cases that was not detected in other samples. The glomerular proteome of FGN cases also contained IgG1 as the dominant immunoglobulin and proteins of the classical complement pathway. Immunostaining with anti-DNAJB9 demonstrated strong and specific staining of the glomerular tufts in a distribution that mimicked the immune deposits of FGN cases.

Conclusion

Our results identify DNAJB9 as a putative autoantigen in FGN and IgG1 effector pathways as likely mediators for the destructive glomerular injury in FGN.

Anti-DNAJB9 shows strong, discrete peripheral capillary wall and mesangial staining in fibrillary glomerulonephritis (A, B), but not in membranous nephropathy (C), immunotactoid glomerulopathy (D), diabetic glomerulopathy (E), or normal controls (F, H) (IHC). By immunofluorescence microscopy, anti-DNAJB9 shows bright peripheral capillary wall and mesangial staining in fibrillary glomerulonephritis (G), but is negative in normal controls (H).

Funding

  • Other NIH Support