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      Treatment with Mycophenolate Mofetil Attenuates the Development of Heymann Nephritis

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          Active Heymann nephritis in the rat is a model of idiopathic membranous glomerulopathy in man. The autoimmune response is directed to gp330, a large epithelial glycoprotein that is expressed on the tubular and the glomerular epithelium. Characteristic of the disease is the presence of immune complexes and complement in the glomerulus and proteinuria. We studied the effect of a new xenobiotic immunosuppressive agent, mycophenolate mofetil, on active Heymann nephritis. Mycophenolate mofetil significantly reduced the production of autoantibodies against gp330 in rats with Heymann nephritis. Glomerular deposition of IgG was not significantly lower in the treated groups than in the untreated groups with active Heymann nephritis, as detected by immunofluorescence staining. Glomerular complement component C3, however, was significantly lower in the mycophenolate mofetil treated rats. Treatment did not completely prevent the disease, but the percentage of rats that developed proteinuria in the treated groups was significantly lower than in untreated Heymann rats. The results of this study show that mycophenolate mofetil influences the T-cell-mediated humoral autoimmune response in active Heymann nephritis and results in a decreased severity of the disease.

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          Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats

          The nephritogenic antigen of Heymann's nephritis (HN) was previously purified from tubular brush-border fractions of rat kidney and found to be a 330,000- mol-wt glycoprotein (gp330). This study was conducted to determine whether gp330 is also present in the rat glomerulus, and, if so, to establish where in the glomerulus it is located. Rabbit polyclonal and mouse monoclonal antibodies were raised against purified gp330, which specifically immunoprecipitated gp330 from solubilized brush-border fractions and specifically stained microvilli and coated invaginations (located at the base of the microvilli) of proximal tubule cells. Accordingly, they were used to localize gp330 by immunoprecipitation and immunocytochemistry in glomeruli of normal Lewis rats. For immunoprecipitation, purified glomerular fractions were prepared from [(35)S]-methionine-labeled kidneys, extracted with Triton X-100, and the extract was used for immunoprecipitation with affinity-purified rabbit polyclonal, or mouse monoclonal, anti-gp330 IgG. Analysis of immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis fluorography indicated that a band corresponding in mobility to gp330 was specifically precipitated. When unfixed cryostat sections were incubated for indirect immunofluorescence with monoclonal or affinity-purified polyclonal IgG, a fine granular fluorescent staining was seen throughout the glomerulus. When aldehyde-fixed cryostat sections were incubated for indirect immunoperoxidase, reaction product was detected only in the epithelial cells and was not seen in the GBM, endothelium, or mesangium. Within the epithelium it was localized to the endoplasmic reticulum, occasional Golgi elements, multivesicular bodies, and coated pits at the cell surface. The reactive coated pits were distributed all along the cell membrane, including the sides and base of the foot processes. Reaction product was detected in the latter location only in sections that had been digested with neuraminidase before antibody incubation. When rats were given rabbit anti-gp330 IgG by intravenous injection and their kidneys stained for direct immunoperoxidase 3 d later, rabbit IgG was seen to be deposited beneath the slit diaphragms and in the coated pits at the base of the foot processes. The immunocytochemical and immunoprecipitation data indicate, in confirmation of the results of others, that the nephritogenic HN antigen is present in renal glomeruli as well as in proximal tubular brush borders. The immunocytochemical results further demonstrate that gp330 is an epithelial, rather than a glomerular basement membrane, antigen. It appears to be synthesized by glomerular epithelial cells and subsequently becomes concentrated in coated pits. As both the endogenous antigen (gp330) and exogenously administered anti-gp330 antibody were localized to coated pits, it seems likely that coated pits located at the base of the foot processes are the sites where the HN antigen (gp330) and circulating antibodies directed against gp330 meet and where immune complexes are formed.
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            Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection

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              Effect of mycophenolate mofetil (RS-61443) on cytokine production: inhibition of superantigen-induced cytokines


                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                April 2000
                15 March 2000
                : 8
                : 2
                : 77-83
                aDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands; bDivision of Nephrology, St. Michael’s Hospital, Toronto, Ont., Canada
                20652 Exp Nephrol 2000;8:77–83
                © 2000 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 50, Pages: 7
                Self URI (application/pdf):
                Original Paper

                Cardiovascular Medicine, Nephrology

                Autoimmune diseases, Mycophenolate mofetil, Heymann nephritis


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