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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

Mercuric chloride induces a transient systemic T-lymphocyte dependent autoimmune syndrome in Brown Norway rats. Two weeks after the first HgCl2 injection maximum serum levels of anti-GBM antibodies and nephrotic range proteinuria are detected. CyA treatment during HgCl2 administration completely prevented these autoimmune phenomena. Moreover, a prolonged unresponsiveness to HgCl2 was induced, lasting for at least 5 weeks after combined pretreatment with CyA and HgCl2. This unresponsiveness could not be adoptively transferred with peripheral lymphoid cells. Suppression of development of HgCl2-induced proteinuria was adoptively transferred with lymphoid cells from HgCl2-treated donors in remission phase. Unresponsiveness to HgCl2, induced by CyA plus HgCl2 pretreatment, could be broken by reconstitution with naive lymphoid cells. These results suggest that the tolerogenic effect of CyA in HgCl2-induced autoimmunity is not mediated by active suppression; instead, the observed unresponsiveness might be due to direct functional deletion of autoreactive T-lymphocytes. A serendipitous finding was the dissociation in time between synthesis of anti-GBM antibodies and development of proteinuria, suggesting a role for cellular effector mechanisms in the induction of proteinuria.
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PMID:Cyclosporin A induces long-term unresponsiveness in mercuric chloride-induced autoimmune glomerulonephritis. 318 May 13

Fluorescence-activated cell sorter analysis was used to study the peripheral lymphocyte populations during mercuric chloride (HgCl2)-induced autoimmune nephritis in the Brown Norway (BN) rat. Sequential studies showed a transient loss of T cells from peripheral blood attributable to decreases in the percentage of T-helper cells. In addition, there was a decrease in the percentage of T-cytotoxic/suppressor cells prior to the appearance of circulating anti-GBM antibodies, followed by elevated levels of T-suppressor cells during down-regulation of the response. This method may allow closer inspection of the events linking changes in T-cell populations and induction and termination of an autoimmune response.
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PMID:Circulating T-cell populations during mercuric chloride-induced nephritis in the Brown Norway rat. 350 19

It has been shown that Brown-Norway rats develop an immune-type glomerulonephritis after treatment with various mercury-containing drugs. Anti-GBM antibodies were involved, at least in some animals. This glomerulonephritis induced a proteinuria. Strong evidence is given, suggesting that most mercury compounds, some of which, such as mercurial antiseptics, are widely used, could induce an immune-type glomerulonephritis. The question therefore arises, whether these drugs can be used any longer.
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PMID:Immune-type glomerulonephritis induced in the Brown-Norway rat with mercury-containing pharmaceutical products. 617 Sep 1

HgCl2 induces the synthesis of anti-GBM Abs with the development of glomerular and interstitial nephritis, as well as proteinuria, in the Brown Norway rat. The development of this autoimmune disease is a consequence of the appearance of an autoreactive T cell subset-inducing activation of B cells. The administration to mercury-treated rats of the mouse anti-human VLA alpha 4 HP2/1 mAb, which cross-reacts with the rat homologue integrin, completely abrogated the interstitial cell infiltrates. As demonstrated by peripheral blood analysis, this effect is not a result of the depletion of circulating leukocytes or leukocyte subsets. Interestingly, the administration of Abs specific for the alpha 4 integrin also highly reduced anti-GBM Ab synthesis, thus preventing detectable glomerular deposits and proteinuria. Our results confirm that in vivo alpha 4 functions in adhesive interaction of circulating leukocytes and vascular endothelium, and is centrally important in the extravasation and migration of T lymphocytes to sites of tissue injury. We also found a complete absence of interstitial cell infiltrates, together with a positive glomerular IgG lineal deposition pattern, when anti-GBM Abs were passively transferred to rats pretreated with anti-alpha 4 mAb, thus indicating an independent role of alpha 4 integrin in both extravasation of immune cells and production of autoantibodies. Furthermore, these in vivo findings provide preliminary evidence for the participation of the VLA-4 integrin in mediating the intercellular interaction of leukocytes regulating the production of Abs, most likely through the existence of additional yet unknown ligand(s).
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PMID:Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin. 805 27

According to its immunopharmacological profile, 15-deoxyspergualin (15-DOS) has been investigated as to its disease-modifying activity on HgCl2-induced glomerulonephritis (GN) and on tubulointerstitial nephritis (TIN) in Brown-Norway rats. Both models are induced autoimmune disorders in which afflicted animals display high levels of serum autoantibodies directed against the glomerular or tubular basement membrane (GBM or TBM), respectively. The diseases are manifested by high serum creatinine and urea levels with severe proteinuria. In the model of HgCl2-GN, administration of 15-DOS clearly led to a reduction of proteinuria and decreased the amount of rat IgG attached to the GBM. Furthermore, a therapeutic effect could be demonstrated when 15-DOS was given after the appearance of clinical symptoms. Not only urine-protein values but also anti-laminin antibodies returned to normal levels. Also in the experimental TIN-model, 15-DOS, either given during the induction phase, or even late in the onset of the disease, strongly prevented the proteinuria of this autoimmune disease and inhibited the formation of autoantibodies to TBN.
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PMID:Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15-deoxyspergualin. 827 49

In Brown-Norway rats HgCl2 induces an autoimmune disease due to a T-dependent B cell polyclonal activation. This disease is marked by the production of numerous antibodies including antiglomerular basement membrane (GBM) antibodies. Rats exhibit a biphasic glomerulopathy with heavy proteinuria. Initially anti-GBM antibodies are found linearly deposited; they precede the appearance of membranous glomerulopathy. Rats recover spontaneously even if HgCl2 injections are pursued, but mechanisms at play are unclear. We have assessed the effects of transplanting the spleen from a BN rat, either at the acme of the disease or at the time of convalescence, into naive BN rats, some of which were then injected with HgCl2. Transplantation of a spleen from HgCl2-injected rats at the acme of the disease dramatically protects BN rats from all the manifestations of the mercury disease. BN rats transplanted with a spleen from HgCl2-injected rats at the time of convalescence only exhibited a typical membranous glomerulopathy with heavy proteinuria but without circulating anti-GBM antibodies. Antilaminin antibodies were eluted from the glomeruli. This study shows that spleen cells from HgCl2-injected rats are able to confer tolerance to HgCl2-induced autoimmunity. It also shows that some B cell clones escape this tolerance. Finally, this study strongly suggests that membranous glomerulopathy, responsible for proteinuria in this model, is related to the presence of antilaminin antibodies.
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PMID:Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the pathogenesis of HgCl2-induced membranous glomerulopathy. 838 32

Autoantibodies to myeloperoxidase (MPO) are present in sera from patients with various forms of vasculitis-associated glomerulonephritis. Evidence for a pathogenic role of anti-MPO antibodies has been provided mainly by in vitro studies. We studied the pathogenic role of autoantibodies to MPO in a rat model of mild immune-mediated glomerular injury. Brown Norway rats were immunized with human MPO in complete Freund's adjuvant or with complete Freund's adjuvant alone. At 2 weeks after immunization, rats had developed antibodies to human and rat MPO as detected by indirect immunofluorescence, enzyme-linked immunosorbent assay, and immunoprecipitation. At this time point, rats were intravenously injected with a subnephritogenic dose of 150 micrograms of rabbit anti-rat GBM. Rats were sacrificed at 4 hours, 24 hours, 4 days, and 10 days after antibody administration. Control immunized rats developed mild glomerulonephritis characterized by slight proteinuria at day 10 (14.8 +/- 8.1 mg/24 hours) and moderate intraglomerular accumulation of ED1+ macrophages. Crescent formation, tuft necrosis, and tubular atrophy were not observed in those rats. In contrast, rats immunized with MPO developed severe glomerulonephritis characterized by the early occurrence of severe hematuria, marked proteinuria at day 10 (76.2 +/- 18.2 mg/24 hours), and massive glomerular deposition of fibrin. Complement and rat IgG were present in insudative lesions, but no linear pattern along the glomerular capillary wall was observed. By light microscopy, severe glomerular lesions were found at day 10 consisting of crescent formation and fibrinoid necrosis of capillary loops. In the interstitium, tubular necrosis and atrophy and marked interstitial mononuclear infiltration were found in conclusion, autoantibodies to MPO severely aggravate subclinical anti-GBM disease demonstrating their in vivo pathogenic potential.
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PMID:Autoantibodies to myeloperoxidase aggravate mild anti-glomerular-basement-membrane-mediated glomerular injury in the rat. 890 58

Using Brown Norway (BN) rats, we isolated and characterized the tubular basement membrane (TBM) antigens that are immunologically common to humans. The renal basement membrane (RBM) of BN rat, as an antigen source, was solubilized with 8 M urea instead of collagenase followed by extraction with 0.5 M NaCl. On frozen section-immunohistochemistry, the autoantibody obtained from BN rats, which had been immunized with human RBM and showed tubulointerstitial nephritis, bound to the TBM, the basement membrane of the Bowman's capsule, and the brush border of the proximal tubules, but not to the GBM of the normal BN rat kidney. Nephritogenic antigens were isolated by immunoaffinity chromatography using Sepharose-bound purified autoantibody. By Western blot analysis of the eluate, bands with molecular weight of 200 kDa and 180 kDa were positively reacted to anti-FX1A (brush border antigen) antibody and were apparently different from the major bands with molecular weight of 145 kDa and 130 kDa. The bands with molecular weight of 145 and 130 kDa showed major cross reactivity with antibodies to fibronectin and laminin. In contrast with these high molecular weight (HMW) bands, the major 60 kDa band with three minor bands showed no reactivity with any type of antibody tested. These results indicated that the non-enzymatic solubilization of RBM is one of the possible procedures for isolating the HMW form of antigens. These antigens may be epitopically modified pre-existing constitutions of the basement membrane and may play a role in the induction of tubulointerstitial nephritis.
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PMID:Isolation and characterization of tubular basement membrane antigen common to humans and rats. 985 23

Brown-Norway (BN) and Dorus Zadel Black (DZB) rats develop a T-cell-dependent membranous glomerulopathy (MGP) with high proteinuria and antiglomerular basement membrane (GBM) autoreactive antibodies (Abs), upon exposure to mercuric chloride (HgCl2). Laminin is an important autoantigenic target of the anti-GBM Abs, absorbing approximately 30% of the anti-GBM reactivity. Although many anti-GBM Abs have undergone isotype switching, it is currently unclear whether affinity maturation occurs during the HgCl2-induced autoimmune response. To address this question we analysed the rearranged immunoglobulin heavy chain variable-region genes (VHDJH regions) of 15 mAbs that were previously obtained from HgCl2-treated rats. Seven of these mAbs exhibit reactivity towards laminin. Our study showed that the VH-gene usage of antilaminin mAbs is largely restricted to the PC7183 VH-gene family (six out of seven). In addition, we demonstrated that at least three out of six laminin reactive and five out of six non-laminin-binding mAbs are encoded by germline VH genes (a total of eight out of 12 mAbs). Of the eight mAbs that are encoded by germline VH genes, seven are of a non-immunoglobulin M (IgM) isotype, indicating that isotype switching has occurred in these mAbs in the absence of somatic mutations. The mutations observed in the VH genes of the four remaining mAbs do not provide strong evidence for antigenic selection. The data support the notion that B cells in this model of MGP are not subjected to affinity maturation and probably result from polyclonal B-cell activation.
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PMID:Immunoglobulin VH-gene usage of autoantibodies in mercuric chloride-induced membranous glomerulopathy in the rat. 1141 7


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