Hiroyuki Ohmuro

Diffuse Proliferative Glomerulonephritis with Hepatitis C Virus-Like Particles in Paramesangial Dense Deposits in a Patient with Chronic Hepatitis C Virus Hepatitis

A 62-year-old man with hepatitis C virus (HCV) infection developed proliferative glomerulonephritis with IgM and C3 deposits. Electron microscopy showed HCV-like particles in the paramesangial dense deposits, which are similar in shape to HCV previously described. These findings suggest HCV-related proliferative glomerulonephritis.

Urinary levels of interleukin-6 and disease activity in patients with IgA nephropathy.

We studied, using ELISA, 27 patients with IgA nephropathy to determine if levels of urinary interleukin-6 (IL-6) might reflect the disease activity. The levels of urinary IL-6 in patients with the advanced stage were significantly higher than those in patients with the mild stage of the disease or in healthy adults. The results showed a significant correlation between the levels of urinary IL-6 and the disease activity, i.e., levels of urinary cast and urinary protein. It was thus suggested that the measurement of urinary IL-6 is useful in evaluating the degree of glomerular injuries and/or prognosis in patients with IgA nephropathy.

Expression of intercellular adhesion molecule-1 and infiltration of lymphocytes in glomeruli of patients with IgA nephropathy

Using immunofluorescence, we studied 19 patients with IgA nephropathy to determine whether the expression of intercellular adhesion molecule (ICAM)-1 in glomeruli might reflect the disease activity. The relationship between the expression of ICAM-1 and the infiltration of lymphocytes, monocytes and polymorphonuclear leukocytes (PMN) in glomeruli of IgA nephropathy cases was examined. The expression of ICAM-1 in patients in the advanced stage was significantly higher than that in patients in the mild stage. In double immunofluorescence, the distribution of ICAM-1 expression in glomeruli was different from that of IgA deposition in patients in both stages. Glomeruli which showed increases of ICAM-1 expression had marked infiltration of lymphocytes (OKT4+, OKT8+ T cells), and monocytes (OKM1+ cells). Increase of urinary protein and decreases in renal function were observed in patients in the advanced stage. It appears that the expression of ICAM-1 is closely linked to glomerular cell proliferation, and infiltration of lymphocytes and monocytes in patients with IgA nephropathy. However, the expression of ICAM-1 in glomeruli might not be correlated with IgA-dominant immune complexes in this disease.

Binding Capacity of Serum IgA to Jacalin in Patients with IgA Nephropathy Using Jacalin-Coated Microplates

Binding capacity of serum IgA to jacalin in 22 patients with IgA nephropathy, 14 patients with diffuse mesangial proliferative glomerulonephritis (non-IgA nephropathy) and 20 age-matched healthy adults was examined by enzyme-linked immunoassay (ELISA) using jacalin-coated microplates. In contrast to previous findings, the binding capacity of serum IgA to jacalin in patients with IgA nephropathy measured by ELISA using jacalin-coated microplates was significantly higher than that in healthy adults. The ratio of serum IgA levels measured by this method to those obtained by single radial immunodiffusion was significantly increased in patients with IgA nephropathy. It appeared that the capacity of serum IgA binding to jacalin was marked in these patients. It is concluded that the binding capacity of serum IgA to jacalin is not ubiquitously impaired in all patients with IgA nephropathy.

Effect of monoclonal antibody CD4 on expression of intercellular adhesion molecule 1 in renal tissues of ddY mice: a spontaneous animal model of IgA nephropathy

Immunofluorescence studies were performed to determine whether the expression of intercellular adhesion molecule 1 (ICAM-1) in ddY mice, a model for IgA nephropathy (Bergers disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of monoclonal antibody CD4. Using immunofluorescence, the mean intensity of IgA deposits in renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control ddY mice of comparable ages. Marked expression of ICAM-1 was observed in glomerular capillary walls and mesangial areas in both control and treated ddY mice aged 40 and 70 weeks. The glomerular mesangial expansion in the treated ddY mice was milder than that found in the control ddY mice. No significant difference in glomerular cell proliferation between the treated and control ddY mice was observed. Although the infiltration of CD4+ T cells in glomeruli was slightly decreased after the treatment, that of CD8+ T cells and macrophages/monocytes was marked in both control and treated ddY mice aged 40 and 70 weeks. Thus, it appears that CD4+ T cells modulate the amount of IgA deposits in glomeruli, and other factors may be involved in the expression of ICAM-1 in glomeruli of IgA nephropathy in ddY mice.

IgA Deposits Might Not Influence the Production of Extracellular Matrix in Glomeruli of ddY Mice, a Spontaneous Animal Model for IgA Nephropathy

Immunofluorescence studies were carried out to determine whether the expression of extracellular matrix (ECM) in glomeruli of ddY mice, a model for IgA nephropathy (Bergers disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules (mAb CD4). This mAb CD4 showed a selective decrease in the number of CD4+ T cells in the peripheral blood of ddY mice as described previously. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of mAb CD4. In immunofluorescence, the mean intensity of IgA deposits in the renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control mice at comparable ages. There was no significant difference in the distribution or intensity of ECM components, i.e. type IV collagen, fibronectin and heparan sulfate proteoglycan, in glomeruli between the mAB CD4-treated and the control ddY mice. In light microscopy, mesangial expansion in the treated ddY mice was milder than that found in the saline control mice. No significant differences in the average number of intraglomerular cells, levels of serum IgA and urinary protein between the treated and control ddY mice were observed. Thus, it appears that although CD4+ T cells modulate the amounts of glomerular IgA deposits, other factors may be involved in the expression of ECM in glomeruli of IgA nephropathy in ddY mice.

A Case of Lupus Nephritis Showing Good Clinical Course and Apoptosis in Glomerular Cells Detected by the Nick End Labeling Method

We report here an adult patient with lupus nephritis who had a good clinical course under long-term observation. Apoptotic bodies in the glomeruli were determined in serial renal biopsy specimens by the nick end labeling method. Apoptotic bodies in the proliferated glomerular cells were detected in the 3rd renal biopsy but not in the 2nd biopsy. The clinical activities of lupus nephritis fluctuated until the time of the 3rd renal biopsy. The 3rd renal biopsy was performed because of increased proteinuria and an increased amount of hyaline, granular and red blood cell casts, with impairment of renal function. The levels of proteinuria, creatinine clearance and serum complements were improved after the 3rd renal biopsy. It appears that apoptosis might control glomerular cell proliferation and also influence the clinical course of lupus nephritis.

Detection of Glycosylated Protein in Renal Tissues and Dermal Vascular Vessels in the Microalbuminuric Stage of Diabetic Nephropathy Using the Nitro Blue Tetrazolium Reaction

Detection of glycosylated protein in renal and dermal tissues was performed in patients in the microalbuminuric stage of diabetic nephropathy using the nitro blue tetrazolium (NBT) reaction. The intensity of NBT staining in glomeruli and dermal vascular vessels was marked in the microalbuminuric stage as well as in the overtly proteinuric stage. The NBT staining in the renal and dermal vascular walls in both stages was significantly stronger than in the samples of control autopsy patients. It appeared that nonenzymatic glycosylation in various tissues, i.e. kidneys and dermal vascular vessels, had already progressed in the microalbuminuric stage in patients with diabetic nephropathy.

Effect of low-protein diet on glomerular changes in ddY mice: a spontaneous animal model of IgA nephropathy.

Yasuhiko Tomino, MD, Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113 (Japan) Dear Sir, Long-term dietary protein restriction is generally considered to reduce the levels of urinary protein and ameliorate the glomerular injuries in patients with various glomeru-lonephritides. We usually start dietary protein restriction after the definite diagnosis, although restriction from an early stage might show a good prognosis in such diseases. The authors reported that the ddY mouse strain can serve as a spontaneous animal model for IgA nephropathy [1, 2]. Marked depositions of IgA and C3 in glo-meruli and glomerular mesangial expansion were observed in the ddY mice after 40 weeks of age [1]. We attempted to compare the glomerular changes between the low-protein and the high-protein diets in ddY mice. Twenty ddY mice were fed a standard diet containing 22% protein until 40 weeks of age. These ddY mice were divided into two diet groups, i.e. low protein (6%) and high protein (50%). ddY mice of both groups were sacrificed at 70 weeks of age. Urinary protein was measured every 2 weeks according to the method of Knight et al. [3]. Renal sections stained with hematoxylin and eosin, and periodic acid-Schiff were examined by light microscopy. Renal cryostat sections were stained with FITClabelled goat anti-mouse IgA, IgG, IgM and C3 antisera at room temperature for 45 min. Type IV and I collagens, ñbronectin and laminin were also stained. The sections were examined using a Fig. 1. a Glomerular enlargement and mesangial expansion were observed in the high-protein diet ddY mouse. PAS. × 400. b These light-microscopic findings were improved in the lowprotein diet mouse. PAS. × 400. c Glomerular deposition of IgA was marked in the high-protein diet ddY mouse. × 400. d The intensity of glomerular IgA deposition was decreased in the lowprotein diet mouse. × 400. KAIIGER E-Mail karger@karger.ch Fax+ 41 61 306 12 34