IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium

Abstract

Fibrillary glomerulonephritis (FGN), a rare disease is pathologically characterized by glomerular fibril accumulation ranging from 12 to 24 nm in diameter with negative Congo red staining. Recently, the identification of DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sensitive and specific marker for FGN has revolutionized diagnosis of this disease. However, few recent studies have reported DNAJB9-negative glomerulonephritis with fibrillar deposits. As such, it remains unclear whether DNAJB9-negative cases can be considered equivalent to FGN. Here, we report the case of a 70-year-old woman who developed renal impairment and nephrotic-range proteinuria. Renal biopsy and pathological examination revealed focal glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed IgA-dominant deposition of polytypic IgG in the glomerulus. Electron microscopy revealed hump-like subepithelial electron dense deposits with fibrils of 15-25 nm in diameter. These findings were consistent with FGN; thus, Congo red and direct fast scarlet (DFS) staining, and immunohistochemistry for DNAJB9 were performed. In addition to negative Congo red/DFS/DNAJB9 staining, laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) resulted negative for DNAJB9, which is a highly sensitive and specific marker for FGN. The patient's renal function further declined, prompting administration of rituximab weekly for 2 weeks, similar to the treatment for FGN. This is a unique case of IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium, unlike previous DNAJB9-negative cases. Thus, DNAJB9-negative cases diagnosed based on accurate electron microscopic evaluation must be gathered, and LMD and LC-MS/MS must be used to analyze the organized fibrillar deposits to reveal the disease entity.

Keywords: DNAJB9; Fibrillar glomerulonephritis; IgA-dominant deposits; Kidney biopsy; Mass spectrometry; Subepithelial deposits.

Fig. 1

Kidney biopsy analysis using light microscopy. Kidney sections under light microscopy show mild interstitial fibrosis and tubular atrophy (a Masson’s trichrome staining, original magnification× 40). The glomeruli show mild mesangial expansion (b Periodic acid-Schiff staining, original magnification × 400). One of the 14 glomeruli showed segmental sclerosis with fibrocellular crescents and segmental endocapillary hypercellularity. (c Periodic acid-Schiff staining, original magnification × 400)

Fig. 2

Immunofluorescence staining of the kidney biopsy: positive immunofluorescence staining for IgG, IgA, IgM, C3, κ, and λ along the segmental capillary walls

Fig. 3

Immunofluorescence staining for IgG subclasses: immunofluorescence staining for IgG subclasses showed that IgG1 and IgG2 were present along the segmental capillary wall and in the mesangial region

Fig. 4

Electron microscopy analysis of the kidney biopsy: electron microscopy showing electron-dense deposits (EDD) in the subepithelial areas (a original magnification × 3000). The EDD shows randomly arranged fibrillar structures (b original magnification × 20,000). The diameter of the fibrils ranged from 15 to 25 nm (c original magnification × 50,000)

Fig. 5

Immunohistochemistry and mass spectrometry findings of kidney biopsy: Negative Congo red staining (a original magnification × 400) and DnaJ homolog subfamily B member 9 (DNAJB9) staining (b original magnification × 400). Result of laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) (c). A specific protein was not identified using LMD and LC–MS/MS