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)

A method for detection of circulating immune complexes by the use of 125I labelled staphylococcal protein A is described. In a polyethylene glycol solution as little as 1-2 mg/l of soluble heat aggregated human IgG could be quantitated. Variables which might influence the assay were examined. Separation of immune complexes in serum from monomeric IgG was essential and achieved by gel chromatography on Sephadex G200. This assay may be suitable for clinical routine for detection and quantitation of immune complexes. A preliminary study on the clinical application of the method is presented. 58% of patients with systemic lupus erythematosus and 42% of patients with rheumatoid arthritis had increased levels of immune aggregates in serum compared to a group of healthy individuals.
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PMID:Detection of circulating IgG aggregates and immune complexes using 125I protein A from Staphylococcus aureus. 78 51

Sera and 5% PEG-precipitates from 20 patients with IMN, 18 with MPGN, 20 with SLE, 8 with anti-GBM disease and 17 with other varieties of glomerulonephritides, 19 patients with chronic liver or intestinal diseases, as well as those from 40 healthy adults, were tested by gel prcipitation for the presence of a ubiquitous tissue antigen (UTA) and/or its corresponding antibody, previously shown to be associated with renal disorders. The antigen was detected in sera of 5 patients with IMN, one with anit-GBM disease and one with SLE. Corresponding antibodies were present in sera of 2 patients with IMN. In 4 of 5 patients with IMN and UTA was only detected if the sera were first treated with PEG (mol. wt. 6,000) which induces precipitation of antigen-antibody complexes and other high molecular weight components in serum. The UTA was not detected in renal glomeruli by immunofluorescence. The possible significance of these findings in the pathogenesis of renal diseases is discussed.
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PMID:A ubiquitous tissue antigen and its corresponding antibody in sera of patients with glomerulonephritides. 82 47

The search for circulating immune complexes by precipitation tests using polyethylene glycol (PEG) was performed on a series of normal and pathological sera. Various factors affecting PEG precipitation were studied. Immunoglobulins and complement factors percipitated by PEG (3.5%) were quantified and their significance was discussed in relation to serum levels. The PEG test was compared to labeled C1q binding test with a fairly good correlation. The direct evaluation of the amount of C4 precipitated with IgG by 3% PEG (C4 test) provided a simpler routine assay than the C1q binding test for detecting complement-fixing immune complexes. The direct PEG test and the C4 tests gave positive results in patients with diseases generally presumed to be associated with immune complexes including systemic lupus erythematosus, acute glomerulonephritis, bacterial sub-acute endocarditis and chronic acitve hepatitis. The demonstration of HBs antigen and antibody after acid dissociation of PEG precipitates from hepatitis B seronegative sera illustrated the fact that PEG does precipitate and thus concentrates circulating immune complexes.
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PMID:Detection of circulating immune complexes in human sera by simplified assays with polyethylene glycol. 88 55

This report describes a technique for the general isolation of immune complexes, based on a combination of gel filtration and affinity chromatography. The first step is the preparation of a globulin-enriched fraction by precipitation with ammonium sulfate at 50% saturation, or of an immune-complex-enriched fraction by precipitation with 5% polyethylene glycol 6000. The enriched fraction is then subfractionated by gel filtration in Ultrogel AcA 34. The immune complexes elute close to the void volume in the macroglobulin peak, separated from monomeric IgG molecules. This peak (sometimes subdivided into two fractions) is then submitted to affinity chromatography on a protein A--Sepharose cooumn. Most immune complexes contain IgG molecules and therefore bind to the column. Almost no protein is bound when normal serum is fractionated according to this method, and no immunoglobulins are detectable in the acid-eluted fraction from the protein A--Sepharose column. In two patients with soluble immune complexes in their sera we eluted immunoglobulin-containing fractions from the column; in one, these fractions had high rheumatoid factor titers; and in the second, with a clinical diagnosis of systemic lupus erythematosus, a similar fraction contained RNA.
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PMID:Isolation of soluble immune complexes by affinity chromatography using staphylococcal protein A--Sepharose as substrate. 91 8

A dynamic estimation of the involvement of the complement system in various diseases was obtained by the direct quantitation of breakdown products of C3 and of properdin factor B. The methods used were based, first on the separation of native and fragmented molecules according to their molecular size through a precipitation with polyethylene glycol and, secondly, on an immunochemical quantitation, using specific antisera for the major antigens of C3 and factor B. The sensitivity and the specificity of these methods were demonstrated by activation of complement in vitro with generation of C3 and factor B fragments. A clinical investigation was carried out in 41 patients with systemic lupus erythematosus (SLE), 31 with membranoproliferative glomerulonephritis (MPGN), 26 with other types of glomerulonephritis, and 6 with severe alcoholic cirrhosis of the liver. The following observations were made: (a) an elevated plasma level of C3d fragment of C3 was found in 68% of SLE patients, in 87% of MPGN patients, in 62% of patients with other hypocomplementemic nephritis, and in 15% of those with normocomplementemic nephritis, but in only 33% of patients with liver cirrhosis and very low levels of C3; (b) a significant difference was observed between the levels of C3 obtained with either anti-"native" C3 or anti-C3c sera for immunochemical quantitation, in patients with SLE or MPGN, indicating the presence of "altered" or fragmented C3 in plasma; (c) an elevated plasma level of Ba fragment of properdin factor B was found in 46% of SLE patients, in 67% of MPGN patients, in 50% of patients with other hypocomplementemic nephritis, and in 9% of patients with normocomplementemic nephritis, while the level of properdin factor B was only slightly decreased in these diseases; (d) in SLE and MPGN there was an inverse correlation between the levels of C3d and Ba and the level of C3 in plasma. The level of these fragments was directly correlated with the clinical manifestations of SLE; (e) some patients with a normal C3 level exhibited an elevated plasma concentration of C3 and factor B fragments, suggesting the coexistence of an increased synthesis with a hypercatabolism of complement components. Therefore, the quantitation of complement breakdown products by simple immunochemical methods provides additional information concerning the involvement of complement in disease and new features for the evaluation of the intensity of immune reactions during immune complex diseases.
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PMID:Complement breakdown products in plasma from patients with systemic lupus erythematosus and patients with membranoproliferative or other glomerulonephritis. 114 31

The 125I-Clq binding test was modified in order to allow for the detection of immune complexes in native unheated human serum. Indeed, heat-inactivation (56 degrees, 30 min) was found to reduce the Clq-binding activity of immune complexes mixed with native serum. This effect was not observed when EDTA was added to the native serum before mixing the immune complexes. The modified 125I-Clq binding test was performed in two steps: first, the tested native serum sample was incubated for 30 min at 37 degrees C with 0.13 M EDTA in order to prevent the integration of 125I-Clq into the intrinsic Clqrs complex, second, 125I-Clq and polyethylene glycol (final concentration 2.5%) were added to this mixture, and further incubated for 1 hr at 4 degrees C. Under these conditions, free Clq remained soluble whereas Clq bound to macromolecular complexes was precipitated. The competitive effect of intrinsic Clq and the interference of other substances such as DNA or bacterial LPS were very limited. The modified Clq binding test was applied to the clinical investigation of 44 patients with systemic lupus erythematosus; and increased Clq binding activity (Clq-BA) was observed in 91% of the samples. The level of Clq-BA was found to be significantly correlated to the DNA-binding capacity and to the decrease of the level of some complement components.
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PMID:Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus. 124 40

Antibodies to DNA can be found in the circulation of the majority of patients with Systemic Lupus Erythematosus (SLE). They are quite specific for this disease, which makes their detection an important diagnostic aid to the clinician. Fluctuations in the level of anti-dsDNA in an individual patient generally parallel the clinical state of that patient. Furthermore, the presence of anti-dsDNA may precede the diagnosis of SLE by more than a year. Four methods relevant for the measurement of anti-dsDNA antibodies are discussed in this paper: the ELISA, the indirect immunofluorescence test on Crithidia luciliae, the PEG assay, and the Farr assay. Each of these methods detects a part of the spectrum of anti-dsDNA antibodies present in the circulation of an individual patient. The ELISA is the most sensitive method, whereas the Farr assay is the most specific for SLE. However, with the latter method only antibodies of a relative high avidity for DNA are detected. Mild forms of SLE, where patients only have anti-dsDNA of a low avidity in their circulation, may easily be missed by this technique. Clinically, high avidity anti-dsDNA is related with the more frequent occurrence of nephritis, whereas low avidity anti-dsDNA antibodies are more often found in patients with central nervous system involvement.
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PMID:Detection of antibodies to DNA: a technical assessment. 128 79

The influence of systemic lupus erythematosus (SLE) patients' sera on lipid accumulation in the cultured smooth muscle cells (SMC) from unaffected human aortic intima was examined. It was demonstrated that the cholesterol uptake in the SMC cultured in the presence of SLE sera is 1.5- to 6-fold higher than in the cells cultured with normal human sera (NHS) obtained from healthy donors. Incubation of the SMC with circulating immune complexes (CIC) isolated from lupus sera by precipitation with 2.5% polyethylene glycol 6000 (PEG) caused a 3- to 4-fold rise in the intracellular cholesterol level. The atherogenic effect of lupus sera, as well as isolated CIC, strongly correlated (r = 0.98) with the low density lipoprotein (LDL) content in the PEG-precipitated CIC. The cholesterol level in cultured SMC also increased 2- to 3-fold when growth medium was supplemented with LDL, DNA, and anti-DNA autoantibodies (IgG) affinity isolated from lupus sera. Using immunofluorescent staining, it was shown that the addition of a DNA-anti-DNA IgG mixture to the growth medium, together with NHS, stimulated LDL incorporation in the SMC. The results of double-label staining suggest the formation of LDL-DNA-IgG complexes which seem to be entrapped in cells more actively than free LDL. The composition of PEG-precipitated CIC was studied by electrophoresis and immunoblotting. Significant amounts of apolipoprotein B, as well as low molecular weight DNA and immunoglobulins, were found in SLE-derived CIC. The data obtained suggest that the atherogenic effect of human lupus sera in vitro is generally due to the appearance of LDL-containing immune complexes. Different mechanisms possibly involved in the lupus atherogenesis are discussed.
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PMID:The atherogenic effect of lupus sera: systemic lupus erythematosus-derived immune complexes stimulate the accumulation of cholesterol in cultured smooth muscle cells from human aorta. 162 41

Antibodies to DNA are quite specific for systemic lupus erythematosus (SLE) and occur in the majority of SLE patients. Therefore, their detection is an important diagnostic aid to the clinician. Detection of anti-dsDNA may precede the diagnosis of SLE by more than a year. Fluctuations in the level of anti-dsDNA in an individual patient may give important information on the clinical status of the patient. Four of the most important methods developed for the measurement of anti-dsDNA antibodies will be discussed in this paper: the Farr assay, the PEG assay, the indirect immunofluorescence test on Crithidia luciliae and the ELISA. They will also be compared with one commercially available (Farr) assay, the Amersham anti-dsDNA kit. Each method, detects a part of the spectrum of anti-dsDNA antibodies produced by a patient. The Farr assay is the most specific for SLE; however, milder forms of the disease in which patients have only low avidity anti-dsDNA may easily be missed by this technique. Clinically, high avidity anti-dsDNA is related more frequently to the occurrence of nephritis, whereas low avidity anti-dsDNA antibodies are found more often in patients with central nervous system involvement. Traditionally, SLE is considered an immune-complex disease, in which inflammatory processes are initiated by local deposition of DNA/anti-dsDNA complexes. More recently, a major role was thought to be played by crossreactions of anti-dsDNA with tissue constituents. Our current view, however, is that such a crossreactivity plays only a minor role; we postulate that binding to glomerular constituents is caused by anti-dsDNA antibodies complexed with DNA and histones.
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PMID:Anti-dsDNA: choice of assay in relation to clinical value. 175 10

Immune-complex-mediated vasculitis is a frequent complication of rheumatoid arthritis and systemic lupus erythematosus. The mechanism of deposition of immune complexes within the vessel wall in these diseases remains unknown, but probably involves other proteins. Fibronectin is a likely candidate since it possesses the ability to bind to collagen, endothelial cells, and possibly immunoglobulins and immune complexes. In this study, the binding of fibronectin to IgG and IgM cryoglobulins, cold soluble IgM, IgG, IgG subclasses and IgG fragments was investigated in the solution phase. Static light scattering, fluorescence anisotropy, fluorescence intensity, and PEG precipitation studies were used to investigate binding under different conditions of temperature and ionic strength. These studies failed to demonstrate significant binding between fibronectin and IgM, IgG, IgG subclasses and IgG fragments under the conditions studied. These findings argue against solution phase binding of fibronectin and immunoglobulins contributing to immune complex vasculitis. The possibility of important surface interactions between these proteins has not been ruled out.
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PMID:Lack of binding between cryoimmunoglobulins, immunoglobulins and fibronectin: implications for immune complex vasculitis. 182 33


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