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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A radioimmunoassay for detection of antitubular basement membrane (TBM) antibodies was set up using a human TBM antigen (mol wt, 70,000 daltons), purified after collagenase treatment of the insoluble membrane by preparative polyacrylamide electrophoresis, and labeled with iodine 125. Free labeled antigens were separated from those bound to immunoglobulins by a 20% polyethylene glycol (mol wt, 6,000 daltons) solution. In the presence of normal human or Brown Norway rat sera, less than 10% of the labeled antigens were precipitated. In the presence of sera or of kidney eluates from rats immunized with human TBM, the precipitation of the labeled TBM antigens reached 73%, but in the presence of sera from two patients presenting with an interstitial nephritis and linear deposits along the TBM only, up to 47% of the same antigens were precipitated. In these two cases, the anti-TBM antibodies were mainly directed against the heteropolysaccharide-containing glycopeptides isolated from TBM, that is, against the noncollagenous polypeptides of the TBM antigens. Anti-TBM antibodies were sought in the sera of 52 normal blood donors and of 11 patients presenting with glomerulonephritis and linear deposits of immunoglobulins. The average percentage (+/- 1 SD) of labeled TBM antigens precipitated in the serum of normal blood donors was 7.1 +/- 1.2. Of the patients presenting with glomerulonephritis and linear deposits along the GBM, 9 out of 11 exhibited anti-TBM antibodies by radioimmunoassay; among these 9 patients, 8 also displayed linear deposits of IgG along the TBM. Absorption of anti-TBM and anti-GMB antibodies with particulate TBM or GBM, with both types of glycopeptides isolated from GBM or TBM, indicated that the anti-TBM antibodies were directed against the noncollagenous polypeptides of TBM but that the anti-GBM antibodies mainly reacted with the collagenous polypeptides of TBM and GBM. Finally, it was found that the sera of 2 patients out of 15 presenting with lupus nephritis contained a significant anti-TBM-binding activity, mainly directed against the noncollagenous material of TBM.
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PMID:Radioimmunologic method for detection of antitubular basement membrane antibodies. 74 71

The pathogenic effect of antitubular basement membrane (TBM) antibodies in anti-TBM interstitial nephritis has been demonstrated. To determine the relative role of sensitized cells in inducing this lesion, lymph node cells (LNC) alone or a combination of LNC and peritoneal exudate cells were transferred from Brown Norway (BN) rats, previously immunized with TBM into unimmunized BN-recipient rats. Cells were transferred directly under the recipients' renal capsules. Although significant tubular lesions were induced by the cells, the lesions were usually mild and always focal. Hence, sensitized cells do not appear to be central to the pathogenesis of anti-TBM nephritis.
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PMID:Role of sensitized cells in antitubular basement membrane interstitial nephritis. 127 20

The target antigen, a 54-kD glycoprotein (gp54), reactive with sera from patients with anti-tubular basement membrane (anti-TBM) nephritis, was isolated from collagenase-digested (CD) bovine TBM. The purified gp54 was shown to be non-collagenous by amino acid analysis, and to be a unique basement membrane component by amino-terminal sequencing. The nephritogenicity of gp54 was demonstrated by immunizing strain XIII guineapigs with purified gp54, and producing anti-gp54 antibody and tubulo-interstitial nephritis. Anti-gp54 antibody, affinity-purified from sera of patients with anti-TBM nephritis, bound by immunoblotting to 54-kD and, to a lesser extent, 48-kD components of partially purified human CD-TBM. Indirect immunofluorescence showed that gp54 was present in the basement membrane of proximal tubules of the kidneys of normal human, cow, rabbit, guineapig and Brown-Norway rat but not in Lewis rat. Immunoelectron microscopy revealed localization of gp54 along the interstitial side of the TBM and its association with interstitial collagen fibres. These results indicate that gp54 is the nephritogenic antigen involved in tubulo-interstitial nephritis, and is unique in chemical characteristics and localization in the kidney.
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PMID:Isolation and characterization of the tubular basement membrane antigen associated with human tubulo-interstitial nephritis. 142 91

The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.
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PMID:Experimental gold-induced autoimmunity. 174 85

In order to study disease mechanisms and potential forms of therapy in glomerulonephritis, a model of experimental autoimmune glomerulonephritis (EAG) has been developed in the rat. We have examined the response of Brown-Norway (BN) rats to a single i.m. injection of collagenase-solubilised homologous (Sprague-Dawley, SD) or isologous (BN) glomerular basement membrane (GBM), with and without complete Freund's adjuvant (CFA). There was a dose-dependent circulating anti-GBM antibody response to all preparations of rat GBM. Animals given either antigen alone at a dose of 2 mg/kg developed circulating anti-GBM antibodies, which reached peak values by 6 weeks (63 +/- 5% following SD GBM; 53 +/- 8% following BN GBM), but did not develop glomerular deposits of IgG or nephritis. Animals given 2 mg/kg SD GBM in CFA developed greater concentrations of anti-GBM antibody by 6 weeks (122 +/- 20%) together with linear deposits of IgG on glomerular and tubular basement membranes (TBM), albuminuria (mean 7 mg/24 h), and variable focal segmental necrotising glomerulonephritis with mild interstitial nephritis. The same dose of BN GBM in CFA produced similar concentrations of circulating antibody (144 +/- 26%), with linear deposits of IgG on GBM but rarely TBM, little albuminuria, and variable mild focal glomerulonephritis. Other strains injected with SD GBM in CFA showed a variable circulating anti-GBM antibody response, which was similar to that of BN rats in PVG and DA rats but lower in LEW and WAG rats. Linear deposits of IgG on the GBM were detected in a proportion of PVG and DA rats, but not in LEW or WAG rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental autoimmune glomerulonephritis induced by homologous and isologous glomerular basement membrane in Brown-Norway rats. 192 7

We utilized a model of experimental interstitial nephritis induced by renal tubular antigen in complete Freund's adjuvant to examine a mechanism of immunologic tolerance produced by priming immunization with tubular antigen in incomplete Freund's adjuvant. Brown Norway rats primed with tubular antigen in incomplete adjuvant do not develop significant nephritis after challenge with antigen in complete adjuvant, and this tolerance can be transferred to naive recipients with donor T cells. These T cells also specifically suppress a delayed-type hypersensitivity response to soluble tubular antigen in recipients immunized to produce disease. This suppression is MHC-restricted and is mediated by OX8+ T cells which bind antigen and bear idiotypes cross-reactive with those on antibodies eluted from the tubular basement membrane. Despite the suppression of histologic disease, tolerized animals were able to produce significant titers of antibodies to tubular basement membrane. Our findings demonstrate an additional strategy for altering the natural history of immune-mediated renal disease, and further refine the characterization of the suppressive effect produced by incomplete Freund's adjuvant.
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PMID:Immunoregulation in experimental interstitial nephritis: immunization with renal tubular antigen in incomplete Freund's adjuvant induces major histocompatibility complex-restricted, OX8+ suppressor T cells which are antigen-specific and inhibit the expression of disease. 241 39

Experimental anti-tubular basement membrane (anti-TBM) disease is an autoimmune interstitial nephritis elicited in susceptible rodents after immunization with renal tubular antigen. The nephritogenic antigen in the immunizing preparation is 3M-1, a 48,000 Mr noncollagenous glycoprotein. The hallmarks of the renal lesion are the presence of anti-TBM antibodies (anti-TBM-Ab) and a dense mononuclear cell infiltrate. The anti-TBM B cell repertoire in this disease was analyzed using a library of 22 anti-TBM mAbs generated in a prototypically susceptible Brown Norway rat. These anti-TBM mAbs were all demonstrated to be 3M-1 specific and their characterization formed the basis for the following observations: (a) The size of the anti-TBM B cell population is estimated at 58 distinct clones; (b) by competitive inhibition criteria, all anti-TBM mAbs recognize the same (or spatially close) epitope(s) on 3M-1. This focused recognition was maintained in spite of considerable variability in affinity. Epitopic dominance could also be demonstrated in human polyclonal anti-TBM antisera from a patient with anti-TBM disease; and (c) a crossreactive idiotype was documented, and antisera directed toward this set of variable region determinants was shown to be effective as a prophylactic regimen to abrogate disease, and as a therapeutic modality to arrest the progression of disease; (d) analysis of VH gene families suggested biased usage of Q52- and 7183-like families, although at least three gene families are used in the anti-TBM-Ab response. Thus, the anti-TBM B cell compartment in BN rats is moderately large, but is primarily focused to a single epitope on the nephritogenic antigen and is associated with a disease-modifying crossreactive idiotype.
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PMID:Clonotypic heterogeneity in experimental interstitial nephritis. Restricted specificity of the anti-tubular basement membrane B cell repertoire is associated with a disease-modifying crossreactive idiotype. 312 29

Purified murine tubular basement membrane (TBM) antigen (molecular weight, 32,000) induced interstitial lesions in Brown Norway (BN) rats. TBM antigen prepared from mice of 3 inbred strains--BALB/c, C3H/He, and C57BL/6--and outbred ddY mice possessed both antigenicity and nephritogenecity. Using these TBM antigens, the roles of humoral and cellular immunity in the development of interstitial nephritis (IN) and the genetic control of the induction of IN in inbred mice were investigated. BALB/c mice were highly susceptible to IN and showed a high antibody response and a high lymphocyte proliferative response to syngeneic and allogeneic TBM antigen, whereas C57BL/6 mice did not. C3H/He mice, in which minimal interstitial lesions developed, showed a high antibody response but a low proliferative response of T cells to TBM antigen. TBM antigen sensitized T cells induced interstitial lesions, but anti-TBM antisera did not do so. Thus, the development of IN seemed to be related closely to cellular immunity. Further studies with their hybrids, backcrosses, congenic mice, and recombinant mice suggested that the induction of IN and the immune response to TBM antigen are controlled by 1 or a few dominant genes, whose loci are within, or closely linked to, the H-2 complex.
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PMID:Autoimmune interstitial nephritis induced in inbred mice. Analysis of mouse tubular basement membrane antigen and genetic control of immune response to it. 340 Jul 74

Only few reports are available on the consequences of chronic oral administration of low doses of mercuric chloride (HgCl2). Forty Brown-Norway rats received 150 micrograms HgCl2/100 g body weight 3 times a week by gavage or by i.m. injection with 100 micrograms twice per week. After 2 weeks of oral HgCl2 administration, the rats lost weight and hair. Phases of proteinuria were observed in weeks 5-8 and then continuously from week 12 until the end of the experiment at week 39. Antibodies binding to renal, intestinal, and vascular basement membrane developed after 2 weeks; circulating immune complexes were detectable in increasing titers starting at week 3. There were linear deposits of IgG, IgM, and IgA in the glomerular basement membrane and tubular basement membrane, and along the intestinal basement membrane. After week 11, the first granular immune deposits were observed in renal and intestinal basement membranes. Light microscopy showed thickening of glomerular basement membrane, mesangial matrix, and tubular basement membrane. In addition, interstitial nephritis was observed in some animals. Interestingly, kidney involvement was as severe in the orally as the i.m.-treated animals.
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PMID:Autoimmune disease induced by oral administration of mercuric chloride in Brown-Norway rats. 353 91

The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (alpha TBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity; NP = 3.1 +/- 0.2 vs. LP = 1.1 +/- 0.3; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.34 +/- 0.02 vs. LP = 0.82 +/- 0.03). Titers of alpha TBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established alpha TBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0 +/- 0.2; creatinine = 1.78 +/- 0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2 +/- 0.3 vs. LP = 1.4 +/- 0.2; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.92 +/- 0.05 vs. LP = 0.97 +/- 0.02). Again, the titers of alpha TBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.
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PMID:Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats. 404 36


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