Potential Target for Fibrillary Glomerulonephritis ID'd

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Fibrillary glomerulonephritis glomeruli exhibit overexpression of DNAJB9 protein.
Fibrillary glomerulonephritis glomeruli exhibit overexpression of DNAJB9 protein.

(HealthDay News) -- Researchers have identified a potential diagnostic and therapeutic target for fibrillary glomerulonephritis (FGN), according to two studies published online in the Journal of the American Society of Nephrology to coincide with presentation at the annual meeting of the American Society of Nephrology.

Surendra Dasari, PhD, from the Mayo Clinic in Rochester, Minnesota, and colleagues analyzed the proteomic content of glomeruli in FGN patient biopsy specimens. The researchers detected DNAJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. FGN glomeruli exhibited a >sixfold overexpression of DNAJB9 protein compared with amyloidosis glomeruli. DNAJB9 was detected in all patients with FGN but not in healthy glomeruli or in 19 types of non-FGN glomerular diseases, indicating that DNAJB9 is an FGN marker with 100% sensitivity and 100% specificity.

Nicole K. Andeen, PhD, from the University of Washington in Seattle, and colleagues used mass spectrometry to define the glomerular proteome in FGN compared with that in controls and non-FGN renal diseases. The researchers identified DNAJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein only in FGN cases. FGN cases had a glomerular proteome containing IgG1 as the dominant Ig and proteins of the classic complement pathway. In FGN 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 FGN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease," Andeen and colleagues write.

References

Andeen NK, Yang HY, Dai DF, MacCoss MJ; Smith KD. DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN. J Am Soc Nephrol. doi: 10.1681/ASN.2017050566 

Dasari S, Alexander MP, Vrana JA, et al. DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GN. J Am Soc Nephrol. doi: 10.1681/ASN.2017030306

Haas M. Glomerular Disease Pathology in the Era of Proteomics: From Pattern to Pathogenesis. J Am Soc Nephrol. JASN.2017080881 [Epub November 2, 2017}

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