Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primate erythrocytes (E) play a central role in clearing potentially pathogenic immune complexes (IC) from the circulation. E capture circulating IC via interaction between C3b and C4b sites, generated on the IC during activation of the complement cascade, and the complement receptor, type 1 (CR1), expressed on E. IC are released from E when C3b and C4b sites on the IC are cleaved by Factor I. The goal of this study was to examine the interactions between human E and model IC in the context of quantitative variations in CR1 expression. IC were prepared by combining murine monoclonal IgG1, IgG2b, or IgG3 anti-dinitrophenyl (DNP) antibodies with DNP-bovine serum albumin. The expression of CR1 on E, obtained from eight healthy donors, was quantified by radioimmunoassay and Scatchard analysis. On the basis of quantitative CR1 expression, preparations of E obtained from different donors at various times were categorized into phenotypic groups expressing high, intermediate, or low numbers of CR1. While there was some variation in the expression of CR1 of individual donors, five of the eight donors remained within the same phenotypic group upon repeated sampling. Surprisingly, when interactions between IC and E were examined in vitro, there was no direct relationship between the number of CR1 per E and the peak magnitude of IC binding to E. When peak binding and release rates were calculated, there was a direct correlation between the number of CR1 per E and the peak binding rate of IC constructed with IgG3 antibodies (IgG3 IC). In addition, there was an inverse correlation between the number of CR1 per E and the peak release rate of IgG2b IC. There was no direct correlation between the quantitative expression of CR1 on E and the peak binding or release rates of IgG1 IC. These data indicate that the quantitative expression of CR1 can affect the interactions between IC and E, but that these interactions are also dependent upon the immunochemical properties of the IC. These findings may be relevant to the pathogenesis of diseases, including systemic lupus erythematosus and AIDS, in which E express reduced numbers of CR1.
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PMID:Relationship between immune complex binding and release and the quantitative expression of the complement receptor, type 1 (CR1, CD35) on human erythrocytes. 829 25

The evaluation of disease activity in systemic lupus erythematosus (SLE) is important for selection of the appropriate therapeutic regimen. In addition to the clinical picture, various laboratory parameters are taken into account. However, no validated criteria for the evaluation of the disease activity in SLE have yet been established. Recently, serum levels of soluble interleukin-2 receptor (sIL-2R) have been proposed as a potential parameter for disease activity in SLE. However, the studies reported on this subject so far have focused mainly on certain subsets of the disease, and the evaluation of the disease activity was based on a very limited number of parameters. In the present study, we determined serum levels of sIL-2R in 23 patients with SLE and 30 patients with discoid LE (DLE). Evaluation of disease activity in SLE was based on a comprehensive scale which considered numerous clinical signs and laboratory parameters. In SLE, serum levels of sIL-2R showed a better correlation with disease activity than all the other parameters investigated, including proteinuria, erythrocyte sedimentation rate, serum globulin concentration, titre of antibodies against double-stranded DNA, serum albumin concentration, serum complement levels and white blood cell count. For the first time, we report on elevated serum levels of sIL-2R in DLE, which also correlated with disease activity.
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PMID:[Soluble interleukin 2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus]. 832 Jan 15

Chronic inflammatory conditions result from or contribute to many diseases. Prominent among them is systemic lupus erythematosus (SLE). Sera of SLE patients contain an array of various auto-antibodies (Ab), including antinuclear Ab of unknown etiologies. The most puzzling is formation of Ab directed against autologous DNA. Our hypothesis was that increased oxidant production causes oxidation of DNA bases, which provide antigenic determinants that elicit antioxidized DNA Ab. To test this hypothesis, we used oxidized DNA nucleoside (5-hydroxymethyl-2'-deoxyuridine [HMdU]) conjugated to bovine serum albumin (HMdU-BSA) as the antigen. The results of the enzyme-linked immunosorbent assay showed that these Abs are sensitively detectable in SLE sera and sera of various other inflammatory autoimmune diseases. The titers of anti-HMdU Ab were significantly higher (p < .01) than those present in the control sera. Anti-HMdU Ab were predominantly of the IgM isotype, with low levels of IgG and no IgA. Anti-HMdU Ab bound to the HMdU-BSA-coated wells in a concentration- and time-dependent manner. That binding was inhibited by HMdU-BSA and to a lesser extent by thymidine-BSA, a normal nucleoside conjugate. The specific binding appears to be inversely related to the age of the patients, but no significant differences were observed between the sexes of the same age.
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PMID:Recognition of oxidized DNA bases by sera of patients with inflammatory diseases. 834 38

Normal mice immunized with bacterial DNA produce high titers of anti-DNA antibodies and represent a new model for autoantibody production in systemic lupus erythematosus. To determine whether DNA immunization can also provoke clinical manifestations of lupus, the occurrence of nephritis in immunized mice was assessed and correlated with levels of anti-DNA as well as antibodies to glomerular antigens. BALB/c mice immunized with Escherichia coli single-stranded DNA in complexes with methylated bovine serum albumin in adjuvant showed increased proteinuria compared to control mice immunized with mBSA alone. Furthermore, DNA immunized mice had significantly greater glomerular proliferative changes and immunoglobulin deposition than control mice. In an in vitro assay, sera from DNA immunized mice exhibited greater binding to glomerular antigens than sera from control mice. Compared to sera, renal eluates from DNA-immunized mice were enriched for anti-DNA and glomerular binding activity. These data indicate that immunization of normal mice with E. coli DNA induces an immune-mediated proliferative glomerulonephritis that is likely secondary to the renal deposition of anti-DNA antibodies.
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PMID:Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA. 837 Jan 82

Sera from 45 patients with lupus nephritis (LN), 63 patients with immunoglobulin A nephropathy (IgA N), and 71 glomerulonephritic controls (including 44 mesangial proliferative glomerulonephritis cases, 14 membranous glomerulonephritis cases, and 13 focal segmental glomerular sclerosis cases), and from 33 normal control subjects were tested by a cellular enzyme-linked immunoabsorbent assay for their anti-endothelial cell antibody (AECA) activity. Compared with normal controls, AECAs of the IgG subtype (AECA-IgG) were detected in LN (P < 0.001) and AECAs of the IgA subtype (AECA-IgA) were detected in both IgA N and LN (P = 0.018 and P < 0.001, respectively). Binding activity of AECA to endothelial cells was inhibited by endothelial cell lysate and fibroblast lysate but not by lymphocyte lysate, double stranded-DNA, or bovine serum albumin. Anti-endothelial cell antibody-positive sera also reacted with fibroblasts. In IgA N, associations were found between the presence of AECA and younger age (P = 0.036), proportion of crescents greater than 10% (P = 0.016), fibrin crescents (P = 0.016), and focal and segmental necrotizing lesions (P = 0.047). In LN, inverse associations were found between the presence of AECA and the duration of disease (P = 0.021), elevated serum creatinine levels (P = 0.020), decreased creatinine clearance (P = 0.043), and frequency of chronic renal failure (P = 0.036). Positive associations were observed between the presence of AECA and active lupus (P = 0.017), anti-nuclear antibodies (P = 0.015), and anti-DNA antibodies (P = 0.041). Our results suggest that AECA may be linked with the pathogenesis of LN and IgA N.
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PMID:Clinicopathologic associations of anti-endothelial cell antibodies in immunoglobulin A nephropathy and lupus nephritis. 837 32

The characteristics, survival rate and risk factors associated with death in patients with end-stage renal failure treated with chronic ambulatory peritoneal dialysis (CAPD) were studied. This is a retrospective study of a cohort of 206 patients, from which the follow-up was complete in 190 patients (92%). Only 16 patients (8%) were lost. The study group is composed of 118 males and 88 females, with a mean age of 39 +/- 15 years. The origin of the renal disease was: unknown in 90 patients (44%); diabetes mellitus in 50 (24%); systemic lupus erythematosus in 16 (8%); obstructive uropathy in 15 (7%); glomerulonephritis in 14 (7%), and miscellaneous in 21 (10%). The average follow-up was 12 +/- 11 months. At the end of study, 66 patients were dead (32%). CAPD was discontinued in 12 (6%). Thirty-eight patients (18%) received kidney transplantation. The survival rate for the whole group was 67 and 48% at 1 and 3 years, respectively. Multivariate survival analysis according to the Cox proportional-hazard model showed that the most powerful predictor associated with high risk of death was low serum albumin levels. According to the Cox model other independent variables significantly associated with increase in the probability of death while on CAPD were advancing age, low serum creatinine concentrations and elevated serum cholesterol levels. These results indicate that the risk factors associated with death in CAPD patients are similar to those observed for hemodialysis patients and suggest that using simple laboratory measurements at the enrollment in CAPD the relative risk of death for each patient can be estimated.
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PMID:Death risk in CAPD patients. The predictive value of the initial clinical and laboratory variables. 841 86

To evaluate further bacterial DNA immunization as a model to study antigen drive in the anti-DNA response, the specificity of induced monoclonal anti-DNA antibodies was characterized. A panel of IgM and IgG monoclonal anti-DNA antibodies was produced from spleen cells of BALB/c mice immunized with single-stranded DNA from E. coli complexed to methylated bovine serum albumin in complete Freund's adjuvant. The binding of these antibodies to DNA and non-DNA antigens was tested by ELISA to assess their range of polyspecificity. These monoclonal antibodies were found to bind to nucleic acid as well as non-nucleic acid antigens, such as beta-galactosidase, cardiolipin, Ro, La and Sm. These studies demonstrate that anti-DNA antibodies from normal mice, although induced by bacterial DNA, may display a broad range of antigen recognition and thus resemble lupus anti-DNA antibodies, many of which are polyspecific, in their pattern of cross-reactivity.
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PMID:The fine specificity of monoclonal anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. 845 83

The effects of indomethacin on urinary protein excretion, levels of serum albumin and renal function were studied prospectively in six patients with systemic lupus erythematosus (SLE) and refractory nephrotic syndrome due to lupus nephritis. Two had membranoproliferative glomerulonephritis, two had diffuse proliferative glomerulonephritis, and one each had mesangioproliferative and membranous glomerulonephritis. All experienced a considerable reduction in urinary protein excretion and an increase in serum albumin. Indomethacin was discontinued in two patients because of side effects, and proteinuria recurred to pretreatment levels. The decrease of proteinuria continued during long-term treatment in three patients. Indomethacin did not cause a permanent decline in renal function. Our results suggest that therapy with indomethacin may be beneficial for the treatment of refractory nephrotic syndrome in selected SLE patients. However, because of potential side effects the administration of indomethacin should be monitored closely.
Lupus 1993 Feb
PMID:Refractory nephrotic syndrome in lupus nephritis: favorable response to indomethacin therapy. 848 64

Preautoimmune New Zealand Black/White (NZB/NZW) mice immunized with Escherichia coli (EC) double standard (ds) DNA produce antibodies that bind mammalian dsDNA and display specificities similar to spontaneous lupus anti-DNA. Since calf thymus (CT) dsDNA fails to induce these antibodies, these results suggest a special potency of foreign DNA in inducing serological manifestations of lupus in a susceptible host. To assess the effects of DNA immunization on clinical manifestations in NZB/NZW mice, we measured renal disease and survival of mice immunized with either (a) EC dsDNA as complexes with methylated bovine serum albumin (mBSA) in adjuvant; (b) CT dsDNA with mBSA in adjuvant; (c)mBSA alone in adjuvant; or (d) unimmunized. After immunization with EC dsDNA, NZB/NZW mice developed significant levels of anti-dsDNA antibodies. Nevertheless, these mice had less proteinuria, nitrate/nitrite excretion, and glomerular pathology than mice immunized with either mBSA alone, CT dsDNA/mBSA complexes, or unimmunized mice. Survival of the EC dsDNA immunized mice was significantly increased compared with the other mice. Furthermore, immunization of mice after the onset of anti-DNA production and proteinuria stabilized nephritis and prolonged survival. The improvement in renal disease occurred despite the expression of autoantibodies that bound mammalian dsDNA as well as glomerular antigens. These results suggest that bacterial DNA has immunological properties that attenuate murine lupus despite the induction of pathogenic antibodies.
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PMID:Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA. 866 97

Previous studies have shown that lipid peroxidative processes may play a role in disease pathogenesis in lupus-prone MRL/lpr mice. Studies were thus performed to determine if an immune response against malondialdehyde (MDA), a highly reactive byproduct of lipid peroxidation, was present in these mice. By using MDA-modified mouse serum albumin (MSA) as antigens in ELISA, we found that these mice produce high levels of MDA-specific antibodies in the complement-fixing IgG2a and IgG2b subclasses. Anti-MDA antibodies were also found in MRL/+ mice but in significantly lower levels. The specificity of these antibodies was verified by inhibition ELISA. MDA may contribute to disease pathogenesis in these mice by altering the immunogenicity of self molecules, eliciting an immune response and forming immune complexes that may deposit in tissues.
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PMID:Antibodies against malondialdehyde (MDA) in MRL/lpr/lpr mice: evidence for an autoimmune mechanism involving lipid peroxidation. 884 52


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