Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiotypes (Id) of human anti-DNA antibodies, designated as O-81 Id, were specifically detected on the immune deposits of renal glomeruli in 46% of patients with lupus nephritis. Id-binding to anti-Id antibodies was blocked by free O-81 Id and to some extent by free DNA. DNase or acid buffer treatment failed to reveal new Id determinants on the deposits. O-81 Id and NE-1 Id activity were also detected on the renal eluate-derived IgG, but not IgM from the autopsy cases with lupus nephritis. The incidences of O-81 Id were not associated with histological features in the glomeruli, but the distribution patterns were similar to those of IgG deposits. Our study also showed that 65% to 70% of patients with IgG deposits either in the subendothelium or in the subepithelial area of the glomerular basement membrane (GBM) showed positive tests for O-81 Id. It was also noted that most patients with massive proteinuria had O-81 Id in their glomeruli. It is concluded that O-81 Id deposits are relatively specific for active lupus nephritis and that immunofluorescence studies using anti-Id antibodies may be clinically useful for specifying the renal lesions of systemic lupus erythematosus (SLE).
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PMID:Anti-DNA idiotypes deposited in renal glomeruli of patients with lupus nephritis. 186 80

Acute glomerulonephritis is characterized by the presence of hematuria, proteinuria and edema, and often hypertension and acute renal failure. Acute post-streptococcal glomerulonephritis is the prototypic disease of acute glomerulonephritis. It is seen after both streptococcal pharyngeal and skin infections with a latency period from infection to presentation of 7-14 days and 14-21 days respectively. Approximately 90 percent of post-streptococcal glomerulonephritis occurs in young children. The diagnosis is made by supporting evidence of recent streptococcal infection, a positive ASO-titer or Anti-DNAase B titer, with associated hypocomplementemia. The disease is self-limited and generally requires only supportive therapy with resolution occurring over a period of weeks to months. There are generally no permanent sequelae in children. Adults may have a higher incidence of hypertension and chronic renal failure as a result of post-streptococcal glomerulonephritis.
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PMID:Acute post-streptococcal glomerulonephritis. 200 61

Inflammatory cell populations in glomerulonephritis (GN) are not well characterized. A method is reported for isolating leukocytes from glomeruli. GN was induced in rats by perfusing left kidneys (LKs) with cationized human IgG followed by intravenous rat anti-human IgG serum. Acute GN developed in LKs with proteinuria, deposition of human and rat IgG and C3, leukocyte infiltration, and capillary wall electron-dense deposits. Glomeruli (GL) isolated at 24 hours were digested with collagenase, trypsin, and DNase, and the resulting cells were as follows (mean +/- SEM): LK, 354 +/- 25/GL; RK, 214 +/- 32/GL. Cells were labeled with monoclonal antibody MRCOX1 (anti-rat leukocyte common [LC] antigen) followed by FITC F(ab')2 rabbit anti-mouse Ig: LK, 170 +/- 11 leukocytes/GL;RK, 8 +/- 2 leukocytes/GL (P less than 0.001). Isolated cells were sorted by flow cytometry to 98% pure LC+ cells with greater than 80% viability (Giemsa staining: 86% mononuclear cells, 14% neutrophils); the ultrastructure was that of maturing macrophages and neutrophils. This method quantitates leukocyte infiltration and provides leukocytes from nephritic glomeruli suitable for in vitro studies.
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PMID:Isolation and characterization of inflammatory leukocytes from glomeruli in an in situ model of glomerulonephritis in the rat. 354 49

Rabbits immunized with ultraviolet-irradiated DNA (UV-DNA) produced high titers of serum antibody. This experimental model was studied to determine if injection of antigen (UV-DNA) intravenously into immunized animals would induce glomerulonephritis and proteinuria. Proteinuria was observed several days after the start of daily intravenous injections into immunized animals and was sustained as long as injections were continued, but fell to normal values after stopping antigen administration. The kidneys showed glomerulitis sometimes associated with focal proliferative lesions, and immunofluorescence showed rabbit Ig and C3 in glomeruli. By electron microscopy, electron-dense subendothelial deposits were seen. Sucrose density gradient analyses of sera immediately after antigen injections suggested the presence of immune complexes of DNA and antibody since both heavy sedimenting and 7S Ig were detected. After digestion with deoxyribonuclease rabbit Ig could be found only in the 7S sedimenting fractions. Intravenous injection of UV-DNA into normal, nonimmune animals did not produce heavy sedimenting Ig or abnormal sedimentation patterns. These studies with an experimental model might provide insight into pathogenetic mechanisms operating in systemic lupus erythematosus where the importance of DNA-anti-DNA immune complexes have been documented. The studies suggested that gradual accumulation of DNA immune complexes in glomeruli might be one mechanism causing renal functional abnormalities.
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PMID:Experimental renal disease induced by DNA-anti-DNA immune complexes. 455 Apr 91

Antibodies to single-stranded DNA (anti-ssDNA) and double-stranded DNA (anti-dsDNA) were determined in serum and urine of nine patients with systemic lupus erythematosus (SLE) presenting with heavy proteinuria (greater than 300 mg/dl), and the activity of anti-DNA antibodies was compared between paired serum and urine samples in each patient. The results were expressed by the anti-DNA activity (radioimmunoassay units per milliliter) divided by the concentration of IgG (milligrams per milliliter), so as to correct for the difference of IgG concentration. Anti-DNA was detected invariably in the serum of these patients (anti-ssDNA/IgG 4.8 to 27.2, anti-dsDNA 5.6 to 107.8). In contrast, anti-DNA activity was not detectable in urine samples from any of the nine patients. The urine samples from these patients, as well as those from normal individuals, were found to contain ssDNA at levels not significantly different from each other (0.25 +/- 0.15 vs. 0.19 +/- 0.07 microgram/mg creatinine, P greater than 0.1). The failure to detect anti-DNA in the urine of SLE patients, however, was not due to the ssDNA contained in the urine, because no anti-DNA activity was detected even after their urine samples had been digested with deoxyribonuclease. On the basis of these results, anti-DNA in the serum of SLE patients was considered to be entrapped in the kidney, probably owing to its binding with DNA deposited in their glomeruli.
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PMID:Entrapment of anti-DNA antibodies in the kidney of patients with systemic lupus erythematosus. 698 73

The pathogenesis of lupus nephritis is felt to be mediated by anti-DNA antibodies. However, the anti-DNA response and renal disease do not entirely correspond. We recently developed a new assay which detects immune elements based on their ability to bind glomeruli as an alternative approach to understanding the pathogenesis of this disorder. The glomerular binding activity (GBA) defined by this assay consists of immune elements containing IgG which interact specifically with renal tissue, the binding of which is DNase-inhibitable, but which do not bind to DNA directly. In the current study we assessed the relationship between GBA and renal disease in MRL/lpr mice (both untreated and cyclophosphamide-treated) and compared it with the anti-DNA assay. Both assays were highly correlated with renal disease in untreated mice in terms of proteinuria. In cyclophosphamide-treated mice, however, only a weak correlation between the anti-DNA assay and proteinuria was apparent. GBA, in contrast, was more strongly correlated with proteinuria in treated mice. This correlation improved substantially when the DNase-sensitive component of the GBA was used. GBA appeared related to, but not covariant with, the anti-DNA response. These results demonstrate that GBA is a better correlate of murine lupus nephritis than the anti-DNA assay, and suggest that the immune elements detected by this assay, the DNase-sensitive component in particular, may be pathogenically important.
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PMID:Serum glomerular binding activity is highly correlated with renal disease in MRL/lpr mice. 837 Jan 69

The effects of recombinant mouse DNase on a well established murine model of spontaneous SLE have been evaluated. Daily intraperitoneal injections of DNase were given to female NZB/NZW F1 mice during the period of disease development from 4 to 7 months of age or at the height of disease activity from the age of 7 months for 3 weeks. This treatment was compared with the injections of diluent and with an immunosuppressive dose of dexamethasone. The effects of treatment were evaluated using the immunological parameters of disease activity (antinucleoprotein antibody, immune complexes, serum immunoglobulins, anti-cardiolipin antibodies), protein-uria, serum creatinine and renal histopathology (light microscopy, immunofluorescence and electron microscopy). The dose of dexamethasone used (1 mg/kg per day from the age of 4 months) was sufficient to suppress the development of lupus entirely. Treatment with DNase starting at the age of 4 months postponed the development of the disease by about 1 months and extended the period from the onset of disease to death by about 30%. Mice treated for 3 weeks during the most active phase of the disease at 7 months of age showed more dramatic effects. Proteinuria and serum creatinine were significantly reduced and renal histopathology was strikingly less severe than in the control group. Immune complexes involving DNA-containing antigens are believed to play a crucial role in the pathogenesis of SLE. DNA-nucleoprotein, even in immune complexes, can be destroyed by DNase. This enzyme therefore provides a rational way to interfere with the disease process. The results reported here encourage a trial of recombinant human DNase in human SLE and lupus nephritis.
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PMID:The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone. 891 61

OBJECTIVE: To test the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic sclerosis (SSc) and to verify a possible association of ANCA with normotensive renal involvement in SSc. PATIENTS AND METHODS: 51 patients affected by SSc, 35 with diffuse scleroderma (dSSc) and 16 with limited scleroderma (lSSc), were tested for ANCA by indirect immunofluorescence (IIF) on human ethanol and formalin-acetone-fixed granulocytes (before and after DNase treatment), by conventional enzyme linked immuno-sorbent assay (ELISA) and by capture-ELISA. RESULTS: Six out of 51 selected SSc patients had ANCA by IIF (11.7%) and five presented a perinuclear/nuclear atypical ANCA pattern. In all cases we only found anti-proteinase3 (aPR3) antibodies. All ANCA positive patients had diffuse form of SSc (17.1%), all were anti-Scl70 positive (aScl70), five patients had proteinuria, three had microscopic haematuria. All ANCA positive patients were normotensive with normal renin plasma levels, the mean erythrocyte sedimentation rate (ESR) was higher in this group compared to the other SSc patients. CONCLUSIONS: Our study shows that aPR3 is not rare in dSSc. According to the clinical and serological findings and to the recent literature, we can hypothesise that when ANCA are found in SSc, an overlapping of scleroderma with systemic necrotizing vasculitis should be suspected.
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PMID:[Anti-proteinase 3 antibodies in diffuse systemic sclerosis (SSc) with normotensive renal impairment: is it suggestive for an overlapping between SSc and idiopathic vasculitis? ] 1246 76

Deoxyribonucleases (DNases) are key enzymes for digesting DNA. Abnormalities in the function of these enzymes may contribute to the development of anti-DNA antibodies in systemic lupus erythematosus (SLE). In this study, we used bovine DNase 1-coated ELISA plates to screen anti-DNase antibodies in SLE patients. About 62% of the sera of SLE patients (63/101) were positive for anti-DNase antibodies compared to only 8% of normal controls (8/98). A positive correlation was also found between the concentrations of anti-DNase and anti-DNA antibodies in sera of SLE patients. Affinity-purified anti-DNase immunoglobulin G (IgG) from pooled sera of SLE patients bound to bovine DNase as well as DNA. A synthetic peptide, corresponding to the catalytic site of DNase, was able to completely inhibit the binding of anti-DNase IgG to DNase. In addition to bovine DNase, the anti-DNase IgG also bound to and inhibited the enzymatic activities of DNase present in streptococcal supernatants and human urine. Immunization of lupus-prone NZB/NZW mice with bovine DNase enhanced the production of anti-DNase and DNA antibodies, and accelerated the occurrence of proteinuria. Taken together, these results suggest that DNase-inhibitory antibodies which recognize a conserved epitope near the catalytic site of DNase may act in the pathogenesis of SLE.
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PMID:Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus. 1292 95

It was shown that IgGs from the sera of 2-7-month-old control non-autoimmune (CBA x C57BL)F1 and BALB/c mice and 2-3-month-old autoimmune prone MRL-lpr/lpr mice (conditionally healthy mice) are catalytically inactive. During spontaneous development of deep systemic lupus erythematosus (SLE)-like pathology a specific reorganization of immune system of these mice leads to conditions associated with a production of IgGs hydrolyzing DNA, ATP and polysaccharides with low catalytic activities (conditionally pre-diseased mice).A significant increase in DNase, ATPase and amylase IgG relative activities associated with a transition from pre-diseased to deep diseased mice is correlated with additional changes in differentiation and proliferation of mice bone marrow haematopoietic stem cells (HSCs) and lymphocyte proliferation in different organs. The highest increase in all abzyme activities was found in mice immunized with DNA, which in comparison with pre-diseased and diseased mice are characterized by a different profile of HSC differentiation and by a suppression of cell apoptosis. Abzyme activities in the serum of pregnant females were comparable with those for pre-diseased mice, but the profile of HSC differentiation and cell apoptosis levels in pregnant and pre-diseased mice were quite different. Right after the beginning of lactation (4 days after delivery) and in a late time of lactation (14 days after delivery) there was an observed increase in cell apoptosis and two different stages of significant change in the HSC differentiation profiles; the first stage was accompanied with a significant increase and the second with a remarkable decrease in abzyme activities. Overall, all mouse groups investigated are characterized by a specific relationship between abzyme activities, HSC differentiation profiles, levels of lymphocyte proliferation, and cell apoptosis in different organs. From our point of view, the appearance of ATPase, DNase activities may be considered the earliest statistically significant marker of mouse spontaneous SLE and a further significant increase in their activities correlates with the appearance of SLE visible markers and with an increase in concentrations of anti-DNA Abs and urine protein. However, development of autoimmune (AI)-reactions and the increase in the sera anti-DNA antibodies (Abs) and in the abzyme activities in pregnant and lactating mice do not associate with SLE visible markers and proteinuria. The possible differences in immune system reorganizations during pre-disease, disease, pregnancy and lactation leading to production of different auto-antibodies and abzymes are discussed.
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PMID:Formation of different abzymes in autoimmune-prone MRL-lpr/lpr mice is associated with changes in colony formation of haematopoietic progenitors. 1763 44


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