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)

Recently, a new radioimmunoassay--the polyethylene glycol (PEG) assay--was introduced to measure antibodies to double-stranded (ds) DNA. In this method, polyethylene glycol precipitation of formed 3H-DNA/antiDNA complexes is used instead of the ammonium sulfate precipitation used in the Farr assay. In contrast to the Farr assay, with which only high-avidity antibodies to dsDNA are detected, the PEG assay also reportedly measures anti-dsDNA of relatively low avidity. We studied whether this gain in antibody measurement results in loss of specificity for systemic lupus erythematosus. When the PEG assay was applied to a selected panel of 440 sera from patients with various well-defined autoimmune diseases and to a group of 197 normal human control sera, matched sex and age to the patients, the method was found to be fairly specific for systemic lupus erythematosus, although the sera from some patients with myasthenia gravis and some with autoimmune liver disease were also found positive. Screening of 352 additional serum specimens, sent to our laboratory for diagnostic reasons, revealed that, with the PEG assay, an extra population of relatively low-avidity antibodies to dsDNA--missed by the Farr assay--was detected. Upon clinical evaluation, we found that the patients in whom such antibodies were detected generally fulfilled a number of the preliminary criteria of the American Rheumatism Association for systemic lupus erythematosus, but that this diagnosis often was not made. We claim that the presence of low-avidity antiDNA characterizes a milder form of the disease in which patients often show only a single clinical feature of the disease. We conclude that results of the PEG assay add valuable diagnostic and clinical information to results obtained by the Farr assay.
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PMID:Specificity in systemic lupus erythematosus of antibodies to double-stranded DNA measured with the polyethylene glycol precipitation assay. 709 63

SS-B antigen was purified from fresh rabbit thymus by ammonium sulfate precipitation and column chromatography with Sephadex G100 and phosphocellulose. The M. W. of SS-B is ranged at 41,000 to 48,000. It does not contain the other extractable antigens, like Sm, RNP, PM-ScL, Scl-70, Jo-1, and PCNA. The purified SS-B antigen only reacts with the CDC standard serum of anti-SS-B antigen only reacts with the CDC standard serum of anti-SS-B antibody by ELISA. The positive rate of the antibodies being 55.1%, 48.3%, 32.8%, 30.8% and 26.3% in SS, SLE, RA, PSS and MCTD respectively. The titers of anti-SS-B antibodies were higher in SS and SLE patients than other connective tissue disease patients. It was found that all of the anti-SS-B antibodies detected were mainly of IgG isotype. Preliminary analysis of clinical date shows that there is no relationship between anti-SS-B antibody and systemic involvement in SS.
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PMID:[The purification of SS-B antigen and detection of anti-SS-B antibodies]. 840 25

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins.
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PMID:Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. 845 67

It has recently been found that in systemic lupus erythematosus (SLE), a multisystem inflammatory disorder characterized by autoantibody production and decreased cellular immune response, increased spontaneous production of IL-10 occurs. The immunomodulator AS101 (ammonium trichloro(dioxoethylene-0,0')tellurate) was previously shown to significantly decrease IL-10 levels in cancer patients and in murine models. This study shows that AS101 inhibits the development of SLE-related autoimmune pathological manifestations. AS101 decreased the spontaneous IL-10 production by mononuclear cells from SLE patients in vitro. In vivo, systemic injection of AS101 to SCID mice transplanted with mononuclear cells from SLE patients significantly decreased serum human IL-10 levels. There was also a decrease in all serum human Ig isotypes, in anti-dsDNA, and in anti-Sm Igs. In the New Zealand Black/New Zealand White/F1 model, AS101 significantly increased serum TNF-alpha and IFN-gamma while decreasing IL-10 levels; these changes were accompanied by a rapid decrease in anti-dsDNA and anti-ssDNA Igs. More importantly, continuous treatment of New Zealand Black/New Zealand White/F1 mice with AS101 for 6 mo led to the development of proteinuria in 30% of the treated mice compared with 100% in PBS-treated mice (p < 0.001). AS101 treatment reduced the level of immmune complex deposition in the glomeruli, prevented glomerular hypercellularity and mesangial expansion and led to a much smaller mean glomerular volume in treated mice (185 +/- 6 vs 428 +/- 47.103 microm3; p < 0.01). We suggest that treatment with a nontoxic immunomodulator such as AS101, previously used in phase II trials on cancer patients, may be an effective therapeutic approach for controlling SLE.
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PMID:Delay in the onset of systemic lupus erythematosus following treatment with the immunomodulator AS101: association with IL-10 inhibition and increase in TNF-alpha levels. 930 Jun 85

Twenty-four hour urine and spot urine samples from 29 patients with metabolic acidosis were collected for evaluation of urine ammonium in relation to urine anion gap, urine osmolal gap (OG) and modified urine osmolal gap (MOG). Their underlying diseases included SLE in 8, RTA in 7, CRF in 6, RPGN in 2 (one with SLE), Lowe syndrome in 2, on acetazolamide in 2, gastroenteritis in 2, and CAH in one. Twenty-three patients had normal serum anion gap (< 14 mmol/L). Their mean CO2 was 13.77 (9.4-17.9) mmol/L, net acid excretion (NAE) was 33.18 +/- 35.36 mmol/24 hour, NH+4 excretion was 29.16 +/- 31.97 mmol/24 hour. Neither the 24-hour urine nor spot urine anion gap correlated with corresponding urine NH+4 with or without adding urine HCO-3 in the calculation. Spot urine NH+4 correlated well with urine OG (r2 = 0.82, p < 0.001) and less with MOG (r2 = 0.339, p < 0.006). The urine osmolality was well correlated with the sum of 2 (Na+ + K+ + NH+4) + urea for both spot (r2 = 0.990, p < 0.001) and 24 hour urine (r2 = 0.907, p < 0.001) collection. Twenty-four hour urine NH+4 did not correlate with the OG or the MOG. There was no correlation between spot urine NH4/Cr ratio and 24 hour urine NH4/Cr ratio (r2 = 0.243, p = 0.53) nor between spot NAE/Cr ratio and 24 hour urine NAE/Cr ratio (r2 = 0.380, p = 0.014). Therefore in the presence of low urine NH+4 (< 100 mmol/L), urine osmolal gap may be used to determine urine NH+4 indirectly with good correlation. Twenty-four hour urine collection is still necessary to assess renal acidification.
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PMID:Comparison of urine anion gap, urine osmolal gap and modified urine osmolal gap in assessing the urine ammonium in metabolic acidosis. 1073 May 27

High avidity anti-dsDNA IgG antibodies are believed to play an important role in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) and therefore attempts have been made to reduce the concentration of these antibodies in the bloodstream of SLE patients. Previously we reported the development of an antigen based heteropolymer (AHP), a bispecific complex prepared by using the avidin-biotin system to crosslink dsDNA to a mAb specific for the human erythrocyte (E) complement receptor. Our studies indicated that this AHP could bind anti-dsDNA antibodies to E and facilitate clearance of these autoantibodies from the circulation of a monkey without E destruction. Here we report an improved covalent crosslinking procedure and purification scheme in which the AHP construct is isolated by precipitation in 50% saturated ammonium sulfate. We used a dsDNA binding dye, PicoGreen, to demonstrate specificity of binding of dsDNA to E via the AHP. The efficacy of the AHP in binding IgG anti-dsDNA antibodies to E was demonstrated in a sensitive and quantitative assay, based on the time resolved fluorescence properties of europium-labeled anti-human IgG mAbs used to probe the E. We also used this assay to screen SLE patient and normal plasmas for levels of anti-dsDNA IgG. The results of this assay correlate very well with the Farr assay, and therefore this approach may be useful in the development of informative and specific assays for a variety of autoantibodies. Treatment of SLE plasmas with E-AHP under conditions close to physiological led to substantial reductions (> or = 90%) in anti-dsDNA titers. It should be possible to test these new AHP for their ability to target and safely remove IgG anti-dsDNA antibodies from the circulation in animal models.
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PMID:A bispecific dsDNAxmonoclonal antibody construct for clearance of anti-dsDNA IgG in systemic lupus erythematosus. 1122 74

Antibodies to DNA (anti-DNA) play an important role in the pathogenesis of systemic lupus erythematosus (SLE). In blood, these antibodies may exist in a free, unbound state or as part of complexes with DNA. Furthermore, circulating DNA may be either complexed or free. Because of the central role of these immunoreactants (anti-DNA and DNA) in the disease, monitoring of their levels could provide valuable information for both clinical and investigative purposes. In these studies, we have explored the use of a DNA-binding dye, PicoGreen, for the detection of circulating DNA, either total or immune complex bound. In addition, we have used this dye for Farr-type antibody assays. Using autoimmune MRL/lpr mice as a model, we have shown that, while the levels of free DNA in the plasma of these mice were comparable with those of normal BALB/c mice, the amounts in complexes precipitable by ammonium sulfate were significantly greater. Furthermore, we showed that Farr assays using PicoGreen reliably detect levels of free anti-DNA, with values correlated with anti-DNA levels by an enzyme-linked immunosorbent assay. Together, our results suggest that a fluorometric dye can accurately monitor DNA and anti-DNA antibody levels in SLE and may provide important information on immunopathogenesis.
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PMID:The use of fluorometric assays to assess the immune response to DNA in murine systemic lupus erythematosus. 1279 Oct 90

Quantitative autoantibody determination has recently can be widely used to confirm the diagnosis of autoimmune diseases, however, there are several problems with the assay methods. As pitfalls in terms of measurement methods, in this report we describe actual examples of a problem related to the analysis and of a large discrepancy between the data obtained by different methods of measurement. In the first example, the reaction solution in the microplate evaporated during the reaction process in automated analysis using an Eitest CA-RF ELISA kit, causing the values in the outermost wells to be significantly higher than in the inner wells. In the second example, there was a large discrepancy between the values obtained when the anti-dsDNA antibody of a systemic lupus erythematosus(SLE) patient was measured by radioimmunoassay(RIA) and by enzyme-linked immunosorbent assay(ELISA). The reason for the discrepancy in the second example may have been related to the method of the RIA, which used 50% ammonium sulfate in the B/F separation, and the possibility that certain patients have autoantibody that recognizes the ELISA solid-phase antigen more strongly. Accordingly, quantitative assay data for anti-dsDNA antibody, which possesses such diversity, should be evaluated with due consideration of the characteristics of the assay method and by checking them against the clinical data.
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PMID:[Pitfalls in laboratory testing for autoantibodies]. 1292 50

Antibodies that recognize DNA (anti-DNA) are part of the autoimmune response underlying systemic lupus erythematosus. To better understand molecular recognition by anti-DNA antibodies, crystallographic studies have been performed using an anti-ssDNA antigen-binding fragment (Fab) known as DNA-1. The previously determined structure of a DNA-1/dT5 complex revealed that thymine bases insert into a narrow groove, and that ligand recognition primarily involves the bases of DNA. We now report the 1.75-A resolution structure of DNA-1 complexed with the biological buffer HEPES (4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid). All three light chain complementarity-determining regions (CDRs) and HCDR3 contribute to binding. The HEPES sulfonate hydrogen bonds to His L91, Asn L50, and to the backbone of Tyr H100 and Tyr H100A. The Tyr side-chains of L32, L92, H100, and H100A form nonpolar contacts with the HEPES ethylene and piperazine groups. Comparison to the DNA-1/dT5 structure reveals that the dual recognition of dT5 and HEPES requires a 13-A movement of HCDR3. This dramatic structural change converts the combining site from a narrow groove, appropriate for the edge-on insertion of thymine bases, to one sufficiently wide to accommodate the HEPES sulfonate and piperazine. Isothermal titration calorimetry verified the association of HEPES with DNA-1 under conditions similar those used for crystallization (2 M ammonium sulfate). Interestingly, the presence of 2 M ammonium sulfate increases the affinities of DNA-1 for both HEPES and dT5, suggesting that non-polar Fab-ligand interactions are important for molecular recognition in highly ionic solvent conditions. The structural and thermodynamic data suggest a molecular mimicry mechanism based on structural plasticity and hydrophobic interactions.
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PMID:Structure of an anti-DNA fab complexed with a non-DNA ligand provides insights into cross-reactivity and molecular mimicry. 1534 Sep 14

Heavy proteinuria may be caused by either increased glomerulal basement membrane permeability or membrane or podocyte structural damage, and also by impairment of secretion-reabsorption tubular processes. The precise composition of modified or degraded urine proteins in proteinuria is not known. However, a possible toxic effect of proteins on tubular cells and disease progression is assumed. In this study, 15 patients with nephrotic proteinuria and other diagnoses (systemic lupus erythematodes with renal involvement (lupus nephritis) and AAV) were analysed by the 2D electrophoresis method. We have studied sample stability during storage, the albumin separation effect on sample analyses using ammonium sulphate, and the effect of proteases on the protein spectrum. In the first step, the proteins were divided by the isoelectric focusing method using polyacrylamide strips (pH 3-10 linear). The second step involved two-dimensional SDS electrophoresis performed in 12% polyacrylamide gel, which separated proteins according to their molecular weight. The proteins were visualized by the silver method. The gels were evaluated by Phoretix 2D expression software 2005. We found out that samples are stable for more than 6 months provided that they are frozen to -80 degrees C. The separation of albumin caused higher lucidity of the urinary proteomes. Without adding protease inhibitors we could detect proteolysis with increased quantity of proteins manifested in the area of about 10 kDa and decreased quantity of proteins detectable in the area with molecular weights about 50 kDa.
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PMID:Study of urinary proteomes in patients with nephrotic syndrome. 1744 95


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