These results indicate that the altered functions of T cells to produce Th2 cytokines and the increased production of IgG4 by B cells in response to these cytokines characterize the immune response in idiopathic membranous nephropathy.
Objective To determine whether a different renal histopathology is associated with the characteristic IgG subclass distribution, and whether a distinct IgG subclass distribution is involved in a unique immunopathological expression, we compared the distributions of glomerular and serum IgG subclasses in diffuse proliferative lupus nephritis (DPLN), membranous LN (MLN), and idiopathic membranous nephropathy (MN).Patients and Methods The glomerular IgG subclass distributions in patients with DPLN(n=7), MLN(n=10) or MN(n=16) were assessed by direct immunofluorescence microscopy. Serum levels of each IgG subclass were quantitated by ELISA in DPLN, MLN, and MN patients, and in normal human sera (NHS) (n=14).Results IgGl, IgG2, IgG3, and, to a lesser degree, IgG4 were similarly present in glomerular deposits in both DPLN and MLN.In contrast, IgG4 was the predominant glomerular IgG subclass in MN. Regarding the serum IgG subclasses, the meanIgG subclass concentrations and the mean proportion of each IgG subclass to the total IgG (%IgG subclass) in DPLNand MLNwere not significantly different from those in NHS,except for the increased %IgGl in MLN.In MN,the mean %IgG4was selectively increased (p<0.01 vs NHS)in association with a slightly elevated IgG4 concentration; however, the meanconcentrations of other IgG subclasses were significantly decreased (p<0.01 vs NHS), and the %IgG subclasses were not significantly different from those in NHS. Conclusions The results indicate that the IgG subclass distribution is not associated with the different renal histopathologies of DPLNand MLN.This study also shows the selective significance of IgG4 in MN,but not in MLN,another form of membranous glomerulopathy. (Internal Medicine 41 : 936-942, 2002)
Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.
Little is known about the pathogenic mechanisms of IgA nephropathy, despite being the most prevalent form of glomerulonephritis in humans. We report in this study that in (New Zealand White (NZW) × C57BL/6)F1 mice predisposed to autoimmune diseases, the expression of a human bcl-2 (hbcl-2) transgene in B cells promotes a CD4-dependent lupus-like syndrome characterized by IgG and IgA hypergammaglobulinemia, autoantibody production, and the development of a fatal glomerulonephritis. Histopathological analysis of glomerular lesions reveals that the glomerulonephritis observed in these animals resembles that of human IgA nephropathy. The overexpression of Bcl-2 in B cells selectively enhances systemic IgA immune responses to T-dependent Ags. Significantly, serum IgA purified from (NZW × C57BL/6)F1-hbcl-2 transgenic mice, but not from nontransgenic littermates, shows reduced levels of galactosylation and sialylation and an increased ability to deposit in the glomeruli, as observed in human patients with IgA nephropathy. Our results indicate that defects in the regulation of B lymphocyte survival associated with aberrant IgA glycosylation may be critically involved in the pathogenesis of IgA nephropathy, and that (NZW × C57BL/6)F1-hbcl-2 Tg mice provide a new experimental model for this form of glomerulonephritis.
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