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Notizen: Background: Incidental IgA deposition in glomerular mesangium exists in 10–20% of autopsy kidneys1,2 or renal allograft donors.3 In the present study, we examined the clinicopathological features of incidental mesangial IgA deposition in renal biopsy from patients with minimal change nephrotic syndrome (MCNS) to understand the significance of mesangial IgA deposition in MCNS and pathogenesis of IgA nephropathy.Patients and Methods: From January 1994 to September 2000, 63 patients were diagnosed with MCNS by renal biopsy at Kidney Center, Tokyo Women’s Medical University. Mesangial IgA and C3 deposition was examined by immunofluorescence staining using frozen sections. The frequency of IgA and C3 deposition in MCNS and clinicopathological features of IgA-positive patients with MCNS were investigated.Results: The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%) (〈link href="#f1"〉Fig. 1). The serum IgA concentration was significantly higher in the IgA-positive patients than in the IgA-negative patients (309 ± 75 mg/dL versus 245 ± 106 mg/dL, P = 0.043) (〈link href="#f2"〉Fig. 2). The urinary red blood cell count was higher in IgA-positive patients than in IgA-negative patients, although not significantly different (11.7 ± 12.7 counts/HPF versus 5.3 ± 4.0 counts/HPF, P = 0.067) (〈link href="#f3"〉Fig. 3). Other clinical parameters (age, sex, amount of proteinuria, serum creatinine and creatinine clearance) were not significantly different. Histologically, no significant differences were observed between IgA-positive and IgA-negative patients in following parameters: grade of mesangial cell proliferation and mesangial matrix increase, extents of tubular atrophy and interstitial fibrosis and grade of vascular sclerosis. After steroid treatment, all 15 patients with mesangial IgA deposition had become complete remission, although three patients once relapsed proteinuria. The haematuria also disappeared after steroid treatment in these patients.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP14:NEP_14_f1"/〉The frequency of mesangial IgA and C3 deposition in MCNS patients (n = 63). The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%).〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP14:NEP_14_f2"/〉The serum IgA concentration of the MCNS patients with and without mesangial IgA deposition. The serum IgA concentration was significantly higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48) (309 ± 75 mg/dL vs 245 ± 106 mg/dL, P = 0.043).〈figure xml:id="f3"〉3〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP14:NEP_14_f3"/〉The urinary red blood cell counts of the MCNS patients with and without mesangial IgA deposition. The urinary red blood cell count was higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48), although not significantly different (11.7 ± 12.7 counts/HPF vs 5.3 ± 4.0 counts/HPF, P = 0.067).Conclusion: The incidental mesangial IgA deposition was frequently observed in MCNS patients (15/60 patients, 23.8%). The phenomenon of mesangial IgA deposition in MCNS patients was related to higher serum IgA concentration and might cause slight haematuria. However, no influence of mesangial IgA deposition was found on the renal function and the clinical outcome of MCNS after treatment.

Notizen: The aim of the present study was to examine the role of CD28-B7 signalling in the development of glomerulonephritis in ddY mice, an animal model for IgA nephropathy. To achieve this aim, we investigated whether the CTLA-4 (CD152) fusion protein, which binds to B7.1 (CD80) and B7.2 (CD86), affects glomerular pathological changes (including IgA deposition), or functional parameters (such as serum creatinine and proteinuria). Each group (n = 4) was given either human CTLA-4 fused with human IgG (CTLA4Ig) or control human IgG1. All treated groups of mice were injected intraperitoneally at a dose of 0.1 mg twice a week for the duration of the study. Mice given control human IgG1 progressively developed typical mesangioproliferative glomerulonephritis, with remarkable glomerular IgA deposits. In contrast, mice treated with CTLA4Ig showed a significant reduction in proteinuria and mesangioproliferative change, with an expansion of the mesangial matrix at 40 weeks of age. The serum IgA levels of these mice were considerably lower than those in mice given the control human IgG1. A direct immunofluorescence study showed the reduction of glomerular IgA deposits in CTLA4Ig-treated mice. We have demonstrated for the first time that the development of spontaneously occurring IgA nephropathy can be prevented in ddY mice by blocking the CD28-B7 interaction using a soluble form of CTLA4Ig. These results suggest that a costimulatory signal via CD28-B7 may play a crucial role in the development and progression of IgA nephropathy.