To understand the regulatory mechanism of apoptosis in human glomerulonephritis, we examined the expression of Fas antigen (CD95) and Bcl-2 in five normal human kidney specimens and 80 tissues from patients with several types of glomerular diseases. These proteins were detected in glomeruli by immunofluorescence. The number of intraglomerular cells positive for Fas antigen was high in Henoch-Schönlein purpura nephritis and lupus nephritis, and that of Bcl-2-positive intraglomerular cells was high in lupus nephritis, focal glomerular sclerosis, and IgA nephritis. Dual-labeling and staining on serial sections indicated that mesangial cells and occasionally infiltrating leukocytes expressed Fas antigen and Bcl-2. In situ hybridization detected Bcl-2 mRNA in glomerular cells. Electron microscopy revealed apoptotic cells and apoptotic bodies in proliferated mesangial areas and within the glomerular capillaries. Fragmented DNA was detected in glomeruli by in situ nick end labeling, the data of which paralleled the number of Fas antigen-positive intraglomerular cells. In mesangial proliferative types of glomerulonephritis, the population of Bcl-2-positive intraglomerular cells, but not that of Fas antigen-positive cells, was significantly correlated with the number of proliferating cell nuclear antigen-positive glomerular cells, the grade of mesangial cell increase, and the magnitude of proteinuria. This study showed that Fas antigen and Bcl-2 are up-regulated in the glomeruli of several types of human renal diseases. Bcl-2 overexpression might play a role in the prolonged proliferation of mesangial cells and glomerular hypercellularity in glomerulonephritis.

We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

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We describe a patient with IgA nephropathy associated with Crohn disease. IgA nephropathy first appeared at the age of 10 years. Combined therapy with prednisolone, cyclophosphamide, warfarin, and angiotensin-converting enzyme inhibitor resulted in clinical improvement over the following year, and remission was maintained. At the age of 13 years, the patient developed Crohn disease and IgA nephropathy recurred. Significant increases in serum IgA were associated with progression of Crohn disease. An elemental diet combined with oral prednisolone resulted in clinical improvement of Crohn disease and in remission of nephropathy and normalization of serum IgA concentration. The clinical course of the two diseases was linked, suggesting a common pathogenetic mechanism involving an IgA immune response to mucosal challenge in the intestine.