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

Two types of lupus mice, NZB/NZW F1 female hybrids and mice with graft-versus-host disease (GVHD), were studied. Histones H3 and H2A were detected by immunofluorescence in glomeruli of 22/22 proteinuric GVHD and 8/12 proteinuric NZB/W F1 female mice; in non-proteinuric animals, 3/5 GVHD and 2/27 NZB/W F1 female were positive. Using antibodies to histone peptides it was shown that mainly the N-terminal regions of histones H3 and H2A were exposed in glomerular deposits. Western blot analysis revealed antibodies to histone subfractions in sera of 33/34 lupus mice that developed proteinuria. This study provides evidence that histones are involved in the pathogenesis of lupus nephritis.
 ...
PMID:Glomerular immune deposits in murine lupus models may contain histones. 145 82

We have investigated the contribution to the autoimmune disease of (NZB x NZW)F1 (NZB/W) mice made by the T cell receptor beta (TcR beta) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this we developed the NZW.TcR beta NZB strain, a NZW congenic line carrying the TcR beta of NZB type, and produced NZB x NZW.TcR beta NZB (NZB/W.TcR beta NZB)F1 mice. We compared the amounts of anti-DNA and anti-histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double-stranded and single-stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR beta NZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene(s) within or closely linked to the TcR beta chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H-2d/H-2z heterozygosity is discussed.
 ...
PMID:Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice. 182 67

A soluble preparation of nucleoprotein (sNP), a complex of native deoxyribonucleic acid (DNA) and histones, was isolated from calf thymus nuclei and labeled with [(125)I]iodide. Isotope-labeled antigen ([(125)I]sNP) was used in a primary binding radioimmunoassay method to detect antibodies to both sNP and native DNA. Sera with antibody to native DNA reacted with the DNA moiety of sNP and bound [(125)I] sNP, but this binding was completely inhibited by addition of unlabeled native DNA. Antibody to sNP which reacted with DNA-histone complex was not inhibited in the radioimmunoassay by addition of unlabeled DNA. Thus, antibodies to sNP and native DNA could be detected and differentiated by use of a single isotopically labeled antigen. In systemic lupus erythematosus (SLE), sera with binding to [(125)I]sNP was present in 21/36 (58%) patients. The majority (18/21) had antibodies to sNP and native DNA present simultaneously, one had antibody only to sNP and two had antibody only to DNA. In contrast, patients with other connective tissue diseases rarely showed binding to [(125)I]sNP. Serial studies on SLE patients showed that high serum binding to [(125)I]sNP paralleled renal disease activity as reflected by the degree of proteinuria. A fall in binding was observed with subsidence of renal disease and reappearance of increased binding coincided with exacerbation. In these patients, antibodies to sNP and DNA appeared or disappeared pari passu suggesting that in addition to the previously demonstrated role of antibody to native DNA, antibody to sNP might also be implicated in the pathogenesis of immunologically-mediated tissue lesions such as SLE nephritis.
 ...
PMID:Relationship between deoxyribonucleoprotein and deoxyribonucleic acid antibodies in systemic lupus erythematosus. 453 38

The pathogenesis of systemic lupus erythematosus is thought to be primarily under genetic control, with environmental factors playing a secondary role. However, it has been shown recently that intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) induces autoantibodies typical of lupus in BALB/c mice, a strain not usually considered to be genetically susceptible to the disease. In this study, the induction of autoimmune disease by pristane was investigated. BALB/c mice receiving pristane were tested for autoantibody production and histopathological evidence of glomerulonephritis. Six of 11 mice developed IgM anti-single-stranded DNA antibodies shortly after receiving pristane and 4 developed IgM anti-histone antibodies, but anti-double-stranded DNA antibodies were absent. IgG anti-DNA and anti-histone antibodies were absent. In contrast, the lupus-associated anti-nuclear ribonucleoprotein/Sm and anti-Su autoantibodies produced by these mice were predominantly IgG. In addition to autoantibodies, most of the mice developed significant proteinuria. Light microscopy of the kidney showed segmental or diffuse proliferative glomerulonephritis. Electron microscopy showed subepithelial and mesangial immune-complex deposits and epithelial foot process effacement. Immunofluorescence revealed striking glomerular deposition of IgM, IgG, and C3 with a mesangial or mesangiocapillary distribution. Thus, pristane induces immune-complex glomerulonephritis in association with autoantibodies typical of lupus in BALB/c mice. These data support the idea that lupus is produced by an interplay of genetic and environmental factors and that unlike the MRL or (NZB x W)F1 mouse models, in which genetic susceptibility factors are of primary importance, environmental factors are of considerable importance in the autoimmune disease of pristane-treated BALB/c mice.
 ...
PMID:Anti-nuclear antibody production and immune-complex glomerulonephritis in BALB/c mice treated with pristane. 747 13

The levels of histone-reactive IgA antibodies in the sera of adult patients with IgA mesangial glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis and idiopathic nephrotic syndrome (minimal change disease+segmental glomerulosclerosis+IgM nephropathy) were evaluated by an enzyme-linked immunosorbent assay. Increased levels of IgA antibodies to all five major histones (H1, H2A, H2B, H3, H4) were found in all four disease groups when compared to normal controls. These histone-reactive IgA antibodies were restricted to the IgA1 subclass and their levels did not correlate with the levels of total serum IgA, nor with serum creatinine, creatinine clearance, and 24-hour proteinuria. Increasing ionic strength resulted in only partial inhibition of the binding to histones and, in individual patients, levels of reactivity with individual histones were usually correlated. This study shows that elevated levels of IgA antibodies reactive with self antigens are present in primary glomerulonephritis and extends previous observations indicating that anomalies of the IgA system occur in various forms of primary glomerulonephritis and are not limited to IgA nephropathy.
 ...
PMID:Histone-reactive IgA antibodies in adult IgA nephropathy and other primary glomerulonephritis. 752 3

Chronic graft-versus-host disease (GVHD) was induced in female (C57 B10S/DBA/2)F1 hybrid mice with two successive injections of lymphoid cells from parental DBA/2 strain. Serial bleedings of 27 GVHD mice were screened with a panel of antigens including the five histones H1, H2A, H2B, H3 and H4, 15 histone peptides, core particles, dsDNA, heat-shock proteins hsp70 and ubiquitin, a branched peptide of ubiquitinated H2A (U-H2A), poly(ADP-ribose) and SSB/La protein. The predominant IgG response to histone peptides was directed against regions 204-218 of H1, 1-25 of H2B and 1-29 of H4. GVHD mice also produced IgG antibodies to dsDNA and chromatin core particles as reported previously. IgG antibodies reacting with dsDNA appeared before antibodies to core particles and histones. Raised levels of antibodies to U-H2A, but not to monomeric ubiquitin, were also found. While the level of antibodies to dsDNA, histones and core particles decreased significantly before the appearance of proteinuria, suggesting their involvement in glomerular injury, the longitudinal pattern of anti-U-H2A peptide response was apparently not linked to the manifestation of lupus nephritis in GVHD mice.
 ...
PMID:Antibodies to DNA, chromatin core particles and histones in mice with graft-versus-host disease and their involvement in glomerular injury. 795 35

Thymopentin (TP-5) is a synthetic pentapeptide that corresponds to the active 32-36 amino acid sequence of the thymic hormone thymopoietin, of which it retains all the immunomodulatory properties. In this study, we have evaluated the effects of long term prophylactic treatment with TP-5 on the clinical, immunological and histological parameters of the SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr (MRL-lpr) mice. TP-5, administered (s.c.) to these mice at the doses of 1, 10 and 100 mg/kg, was given daily, five times a week, from the 9th to the 26th weeks of life. The prophylactic treatment with TP-5 prolonged in a clear dose-dependent fashion the lifespan of MRL-lpr mice as compared with PBS-treated control mice, and the effect reached statistical significance at the doses of 10 and 100 mg/kg. In parallel ex vivo studies, this clinical effect was associated with multiple profound modifications of the immune system including: (i) the reduction of the spontaneous and Con A-induced release of interleukin-4 (IL-4); (ii) the increased secretion of interferon-gamma (IFN-gamma) and IL-6 upon polyclonal mitogenic stimulation, and (iii) the amelioration of the defective Con A-induced lymphoproliferative response. In contrast, although the drug diminished the severity of proteinuria in MRL-lpr mice, it neither reduced histological signs of lupus nephritis nor diminished the serum titres of anti-native DNA and anti-histone autoantibodies. These results indicate that TP-5 displayed powerful immunodulatory activities in a well known model of human SLE.
 ...
PMID:The effects of thymopentin on the development of SLE-like syndrome in the MRL/lpr-lpr mouse. 797 60

To gain insight into the mechanisms of autoantibody induction, sera from 40 patients with systemic lupus erythematosus (SLE) were tested by ELISAs for antibody binding to denatured individual histones, native histone-histone complexes, histone-DNA subnucleosome complexes, three forms of chromatin, and DNA. Whole chromatin was the most reactive substrate, with 88% of the patients positive. By chi-square analysis, only the presence of anti-(H2A-H2B), anti-[(H2A-H2B)-DNA], and antichromatin were correlated with kidney disease measured by proteinuria > 0.5 g/d. SLE patients could be divided into two groups based on their antibody-binding pattern to the above substrates. Antibodies from about half of the patients reacted with chromatin and the (H2A-H2B)-DNA subnucleosome complex but displayed very low or no reactivity with native DNA or the (H3-H4)2-DNA subnucleosome complex. An additional third of the patients had antibody reactivity to chromatin, as well as to both subnucleosome structures and DNA. Strikingly, all sera that bound to any of the components of chromatin also bound to whole chromatin, and adsorption with chromatin removed 85-100% of reactivity to (H2A-H2B)-DNA, (H3-H4)2-DNA, and native DNA. Individual sera often bound to several different epitopes on chromatin, with some epitopes requiring quaternary protein-DNA interactions. These results are consistent with chromatin being a potent immunogenic stimulus in SLE. Taken together with previous studies, we suggest that antibody activity to the (H2A-H2B)-DNA component signals the initial breakdown of immune tolerance whereas responses to (H3-H4)2-DNA and native DNA reflect subsequent global loss of tolerance to chromatin.
 ...
PMID:The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. 804 Feb 59

IgG antibody specific to double-stranded DNA (dsDNA) has been recognized as a predictive indicator of the renal involvement in systemic lupus erythematosus. However, we recently experienced two cases of overt lupus nephritis without IgG anti-dsDNA antibody. In both cases, high titers of antibody to the histone dimer (H2A-H2B)-dsDNA complex were detected. They responded well to the corticosteroid therapy, with a cytotoxic agent in one case, and the titers of anti-(histone-DNA) antibody was decreased along with the improvement of proteinuria. Based on the recent reports suggesting a pathogenic role of this antibody in lupus nephritis, we suggest that measurement of the anti-(histone-DNA) antibody is necessary in lupus nephritis patients, especially when IgG anti-dsDNA antibody is not detectable.
 ...
PMID:[Two cases of lupus nephritis having a high titer of anti-(histone-DNA) complex antibody without IgG anti-dsDNA antibody]. 875 39

Reactivity of serum antibodies with heparan sulfate (HS) has been associated with human and murine lupus nephritis, although the aetiological significance of this association is not clear. Recent work from our laboratories showed that binding of these antibodies to HS could be mediated by histone containing immune complexes. In human lupus nephritis we found a strong decrease in HS staining in the glomerular basement membrane (GBM). The aim of this study was to elucidate the correlation in experimental systemic lupus erythematosus (SLE) between albuminuria, staining of HS in the GBM and anti-DNA and anti-HS reactivity in plasma. We therefore studied NZB/W F1 mice during different stages of glomerular disease and compared them with age matched control NZB/W F1 mice without albuminuria. Anti-DNA and anti-HS reactivity were measured in longitudinally collected plasma samples and correlated with the onset of albuminuria, staining of HS in the glomerular basement membrane and deposition of immunoglobulins (Ig). HS staining was significantly decreased in the glomerular capillary loops of mice with prolonged proteinuria in comparison with age matched control mice (P = 0.0013). This decreased HS staining was correlated with increased Ig deposition in the capillary loops (tau = -0.42, P < 0.001), albuminuria (tau = -0.508, P < 0.001) and a decreased in anti-DNA levels measured in plasma (tau = 0.758, P < 0.005). Altered anti-HS reactivity in plasma did correlate with increased Ig deposition in the kidney (tau = 0.33, P < 0.05) but was not correlated with decreased staining of HS in the kidney. In conclusion, our study demonstrates that disappearance of staining of HS in the glomerular capillary loops is associated with albuminuria, increased Ig deposition in the glomerulus and decreased anti-DNA reactivity in plasma. Our findings are compatible with a model in which interaction ('masking') of HS with immune complexes consisting of anti-DNA antibodies and nucleosomes takes place.
 ...
PMID:Heparan sulfate staining of the glomerular basement membrane in relation to circulating anti-DNA and anti-heparan sulfate reactivity: a longitudinal study in NZB/W F1 mice. 884 53


1 2 3 4 Next >>