Infantile immunoglobulin A nephropathy showing features of membranoproliferative glomerulonephritis.

Immunoglobulin A nephropathy (IgAN) showing predominant IgA and complement 3 (C3) deposition on the mesangium is an immune complex-mediated glomerulonephritis. This renal disease is the most common primary glomerular disease worldwide. However, infantile onset of IgAN is rare. In the present patient, urinary protein and occult blood were detected in a girl aged 1 year and 8 months on urinalysis at a nursery school. Despite being young, a kidney biopsy was performed for diagnosis and the correct choice of therapy. Glomerular mesangial cell proliferation and a double contour of the glomerular basement membrane (GBM) resembling a railroad track were noted on light microscopy. Therefore, the patient was diagnosed morphologically with membranoproliferative glomerulonephritis (MPGN), because mesangial hypercellularity and thickening of the GBM were identified. However, on immunofluorescent staining, the deposition of immune complexes mainly consisting of IgA, IgG, and C3 was noted in the mesangial region and glomerular capillary loops. On electron microscopy, electron-dense deposits were recognized in the subendothelial and paramesangial regions associated with mesangial cell interposition into the subendothelial space. Autoimmune diseases and infection-associated secondary glomerulonephritis were clinically excluded, because there were no relevant signs or symptoms. Steroid treatment was initiated and findings of urinalysis were normalized within 8 months. This patient was finally diagnosed with IgA nephropathy showing the features of MPGN. The present patient was the youngest among reported cases of IgA nephropathy, suggesting that early onset of IgAN is associated with an MPGN-like lesion. The present report provides information for pathogenesis of IgA nephropathy.

Galactosialidosis associated with IgA nephropathy: morphological study of renal biopsy.

Galactosialidosis is an autosomal recessive lysosomal disease associated with a deficiency of beta-galactosidase and neuraminidase. Described herein is the case of a young adult who had been diagnosed with galactosialidosis at 8 years of age. At the age of 30 years, proteinuria and hematuria appeared and the patient underwent a renal biopsy 1 year later. Light microscopy of the kidney sections indicated fine granular contents in the cytoplasm of glomerular endothelial and epithelial cells, arteriolar smooth muscles and proximal tubular epithelial cells on periodic acid silver-methenamin (PAM) stain. Electron microscopy of these cells indicated enlarged, smooth endoplasmic reticulum and lysosomes containing 150 nm-wide rods with a fine lattice structure at 66 A periodicity. Moreover, electron-dense deposits were located in the paramesangial area. Immunofluorescence staining indicated diffuse and global anti-human IgA and C3-positive staining as a mesangial pattern. Given these findings this patient was therefore diagnosed with both galactosialidosis and IgA nephropathy. This is the first report to describe light and electron microscopy observations of storage materials in the kidneys in young/adult galactosialidosis.

Identification of ID2 associated with invasion of hepatitis C virus-related hepatocellular carcinoma by gene expression profile.

Portal vein invasion (PVI) is a hallmark of metastatic potential of hepatocellular carcinoma (HCC) and is frequently found at a stage of moderately differentiated HCC. To identify genes involved in PVI of HCC associated with hepatitis C virus (HCV), we performed a comprehensive analysis of 12,600 genes in 35 moderately differentiated HCV-related HCCs by DNA microarray. Our supervised learning method identified 35 genes involved in PVI. Among the 35 identified genes, we focused on the inhibitor of DNA binding 2 (ID2), because it encodes a liver-rich dominant-negative helix-loop-helix protein. The microarray results for ID2 were reproduced by quantitative real-time reverse transcription (QRT)-PCR and Western blot analyses. In an independent set of HCV-related HCCs (n=28) and HCV-unrelated HCCs (n=14), our QRT-PCR showed that decrease in ID2 mRNA levels were associated with PVI in HCV-related HCC but not HCV-unrelated HCC. In conclusion, our results strongly suggest that ID2 plays an important role in PVI process of HCV-related HCC.