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)

We have studied the conditions of in vitro binding of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) to fibrinogen and applied the results to identify and measure the serum inhibitors to the binding. For the enzyme-linked immunosorbent assay, platelet extract was delivered to a fibrinogen-coated microtiter plate that was incubated for 2 hours, followed by incubation with anti-GPIIb/IIIa monoclonal antibody for another 2 hours. The plate was then incubated with peroxidase-conjugated anti-mouse IgG for color development. The binding was shown to be calcium-dependent. The binding was partially blocked by treating the coated fibrinogen with anti-fibrinogen antibody. Reduction or dissociation of GPIIb/IIIa resulted in the total loss of its ability to bind to fibrinogen. Platelet extracts of patients with hemophilia showed decreased binding (25% and 14%, compared with control platelet extract), and an extract from a patient with Glanzmann's thrombasthenia showed no binding. With the enzyme-linked immunosorbent assay we have measured serum inhibitors to GPIIb/IIIa binding to fibrinogen in 35 hemophilia A, 17 immune thrombocytopenic purpura, 22 human immunodeficiency virus-related immune thrombocytopenic purpura, and 29 systemic lupus erythematosus serum samples. In those patients with inhibition by serum, polyethylene glycol precipitation of circulating immune complexes (CICs) decreased the inhibition by the supernatants, and all the resolubilized CIC precipitates demonstrated inhibition, which indicates that CICs play a major role in the inhibition of GPIIb/IIIa binding to fibrinogen. This, then, provides evidence of CIC-mediated impaired GPIIb/IIIa binding to fibrinogen in hemophilia A, HIV-ITP, and SLE.
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PMID:Inhibition of platelet GPIIb/IIIa binding to fibrinogen by serum factors: studies of circulating immune complexes and platelet antibodies in patients with hemophilia, immune thrombocytopenic purpura, human immunodeficiency virus-related immune thrombocytopenic purpura, and systemic lupus erythematosus. 200 77

In 353 sera (from healthy donors as well as patients suffering from rheumatoid arthritis, systemic lupus erythematosus, hepatitis, malignant melanoma) circulating immune complexes were determined by C1q-binding test and a C1q solid-phase ELISA. Using peroxidase-labelled antibodies (from rabbit) against human mu-, gamma-, and alpha-heavy chains, the immunoglobulin classes in the complexes were determined. In rheumatoid arthritis, immune complexes contain IgM more frequently (41.5%) than in systemic lupus erythematosus (10%). Immune complexes containing only IgA as immunoglobulin were found in 24 cases. Our results including binding experiments with chemically aggregated IgA suggest, that the binding of C1q to IgA is not necessarily followed by classical complement activation.
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PMID:[Determination of circulating immune complexes and of their component immunoglobulin classes M, G, and A with a C1q-ELISA]. 206 29

This review presents a unifying hypothesis that provides a connection between several types of hypersensitivity reactions associated with several types of drugs and explains some of the therapeutic effects (antiinflammatory activity and antithyroid effects) of these same drugs. This hypothesis centers on the oxidation of these drugs to chemically reactive metabolites by peroxidases. The drugs of interest have functional groups that are easily oxidized. The major peroxidase involved in this hypothesis is MPO because of its critical location in leukocytes which play a key role in the function of the immune system. However, thyroid peroxidase can probably also oxidize many of the same drugs to reactive metabolites, and this may be responsible for the thyroid autoimmunity observed in connection with some hypersensitivity reactions. Peroxidases have also been described in the skin and in platelets, and their presence may be responsible for the high incidence of skin reactions in the hypersensitivity response and the occurrence of immune-mediated thrombocytopenia, respectively. Involvement of other peroxidases, such as prostaglandin peroxidase, may also be important for antiinflammatory effects of drugs. In addition, leukocytes contain prostaglandin synthetase, and the activation of leukocytes leads to the release of arachidonic acid and the production of prostaglandins. This process may also lead to the metabolism of drugs to reactive metabolites. In studies of the metabolism of procainamide and dapsone, aspirin and indomethacin did not inhibit the formation of the hydroxylamine by neutrophils and mononuclear leukocytes. This is evidence against the involvement of prostaglandin synthetase in these oxidation; however, preliminary studies with other drugs suggest that prostaglandin synthetase may contribute to the metabolism of some drugs by leukocytes. Furthermore, the metabolism of phenylbutazone, phenytoin, and tenoxicam, as well as our preliminary work with other drugs such as carbamazepine, suggests that the range of drugs that are metabolized to reactive metabolites by peroxidases may be broader than initially suspected. There are several other drugs that do not fit into the functional group classes covered in this review but have similar properties. A good example is alpha-methyldopa, which is associated with drug-induced lupus, immune-mediated hemolytic anemia, and other hypersensitivity reactions. Such drugs may also be metabolized to reactive metabolites by peroxidases. Another aspect of the hypothesis is that an infection, or other inflammatory condition, may be an important risk factor for a hypersensitivity reaction because such a stimulus leads to activation of leukocytes which can lead to formation of reactive metabolites from certain drugs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Drug metabolism by leukocytes and its role in drug-induced lupus and other idiosyncratic drug reactions. 217 25

The authors provide the results of studying the methodologic characteristics and of the clinical trial of the C1q-ELISA for detection of the circulating immune complexes. The C1q-ELISA is shown to have a high sensitivity and to make it possible to identify 3 micrograms/ml and more of aggregated gamma-globulin. The method can use for detection of CIC E (ab')2-fragments of antibodies to IgG of man and protein A labeled with peroxidase. Using the method, the circulating immune complexes were identified in the sera of 50% of patients with systemic lupus erythematosus, of 30% of patients with dilated cardiomyopathy and of 53% of patients with nonspecific aortoarteritis. It is concluded that the C1q-ELISA can be used in clinical practice for detecting the circulating immune complexes in different diseases of man.
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PMID:[Use of solid-phase Clq-ELISA for detecting circulating immune complexes in human diseases]. 247 7

This study describes an assay for the detection of cytotoxicity for thyroid cells in serum of patients with autoimmune thyroiditis. Quantitative measurement may be performed by DNA or [3H] leucine incorporation determinations. The cytotoxic effect is localized in the gamma-globulin fraction, and is complement-mediated. It is thyroid specific i.e. it is not observed with fibroblasts and patients with other autoimmune diseases (patients with lupus erythematosis or glomerulonephritis) do not have cytotoxic antibodies directed against thyroid cells. The thyroid cytotoxicity is related to the presence of antimicrosomal antibodies and the effect of circulating antibodies is inhibited by human thyroid peroxidase. These results strengthen the possible implication of circulating antithyroid peroxidase antibodies in thyroid damage observed in autoimmune thyroiditis.
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PMID:Cytotoxic assay of circulating thyroid peroxidase antibodies. 249 49

Enzyme-linked immunosorbent assay (ELISA) was developed for determination of serum antiplatelet antibodies. Platelets obtained from healthy donors of blood group 0(1) were washed off plasma and sedimented on the bottom of microtest wells. After washing off unattached platelets and blocking of plastic with albumin platelets were incubated with sera under investigation and binding of serum antibodies was detected using antihuman immunoglobulin antibodies conjugated with peroxidase. Ten patients with idiopathic thrombocytopenic purpura (ITP). 1 patient with systemic lupus erythematosus. 1 patient with red blood cell aplasia and 9 healthy donors (negative control) were studied by ELISA. Serum antibodies which effectively bound to platelets were detected in 5 patients with ITP, in patient with lupus erythematosus and in patient with red blood cell aplasia.
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PMID:[Determination of antithrombocyte antibodies in the blood serum of patients with idiopathic thrombocytopenic purpura by an immunoenzyme method]. 249 66

A method for detection of anticardiolipin (ACL) antibodies with enzyme-linked immunosorbent assay was developed. Microtitre plates were coated with cardiolipin at a concentration of 20 micrograms/ml by evaporation under 4 degree centigrade overnight. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (FCS/PBS) for 2 hours at room temperature. Sera (50 microliters/well) at a dilution of 1:100 were incubated for 2 hours at room temperature. Horseradish peroxidase conjugated rabbit anti-human IgG, IgM, IgA at a dilution of 1:2000, 1:1000, 1:500 respectively was added to the wells, and incubated for one and half hours at room temperature. The results were read at 490nm after incubation with substrates at 37 degree centigrade. 85 patients with systemic lupus erythematosus (SLE), 45 with rheumatoid arthritis (RA), 25 with progressive systemic scleroderma (PSS), and 18 primary Sjogren's syndrome were tested. The frequency of ACL antibody in SLE (48%) was much higher than that in RA (11%), PSS (12), SS (5.5). Three isotypes of ACL (IgG, IgM, IgA) were detected in the study with predominance of IgG isotype. ACL antibody was significantly associated with thrombosis, cutaneous vasculopathy, thrombocytopenia, and spontaneous abortion in patients with SLE. Strong relationship between ACL antibody and lupus anticoagulant was found. There was no correlation between ACL and anti-DNA antibodies, nor was ACL and VDRL test. The level of ACL antibody could be reduced by use of corticosteroids.
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PMID:[Measurement of anticardiolipin antibodies and its significance in systemic lupus erythematosus]. 250 Mar 15

In order to evaluate the contribution of cellular immune mechanisms in the pathogenesis of immune complex-mediated glomerulonephritis, renal biopsies from 18 patients with lupus glomerulonephritis and 26 with cryoglobulinaemic glomerulonephritis were studied. Leucocyte profiles including T cell subsets and 'activated' macrophages within both glomeruli and interstitium were determined, using a panel of monoclonal antibodies as markers, and a sensitive 4-layer peroxidase technique to localize these within tissues. The infiltrating leucocytes were correlated with clinical, histological and immunological parameters of disease activity. Normal glomeruli contained few leucocytes though normal interstitium did (145 +/- 30 mm2), made up predominantly of T lymphocytes and macrophages. There was a significant increase in intraglomerular leucocytes in both systemic lupus erythematosus 4-fold, and essential mixed cryoglobulinaemia 7-fold, as compared to normal. These leucocytes consisted mainly of macrophages, and particularly in cryoglobulinaemia of 'activated' macrophages as demonstrated by their surface expression of the procoagulant tissue factor recognized by the A13 monoclonal antibody. In cryoglobulinaemic glomerulonephritis (GN) there was also a significant increase in T lymphocytes due to a predominance of suppressor-cytotoxic cells (OKT8+). There was a significant increase in interstitial leucocytes in both diseases, lymphocytes (mainly OKT8+ve), and macrophages (mainly 'activated' A13+ve). There were significant positive correlations between disease activity and interstitial leucocyte infiltration including, in lupus nephritis, degree of proteinuria and total leucocytes, hypocomplementaemia and T lymphocytes, increased numbers of monocytes and lymphocytes with a higher histological index of activity, and in cryoglobulinaemic GN of T lymphocytes and proliferative lesions, and T lymphocytes and C1q deposition. This study has demonstrated the importance of the interstitium in the pathogenesis of both diseases, delineated the presence of both T lymphocytes and activated monocytes which make cell-mediated immune mechanisms feasible, and linked the presence of immune mediators to disease activity.
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PMID:The relationship of infiltrating renal leucocytes to disease activity in lupus and cryoglobulinaemic glomerulonephritis. 317 97

A microplate-adapted polyclonal IgM-rheumatoid factor enzyme-linked immunosorbent assay (pIgM-RF ELISA) for the detection of circulating immune complexes (cIC) is presented. The assay involves the competitive binding of cIC and horseradish peroxidase conjugated aggregated human IgG (HRP-AHG) to solid-phase bound polyclonal IgM-RF (pIgM-RF). Aggregated human IgG (AHG) inhibited the binding of HRP-AHG to pIgM-RF in a dose-dependent way. The detection limit of the assay was about 125 ng AHG/ml diluted serum. The coefficients of variation for the assay varied from 5.0 to 14.7% for intra-assay runs and from 4.5 to 13.8% for inter-assay runs. The levels of cIC in sera from 29 patients with systemic lupus erythematosus (SLE), 85 untreated patients with breast cancer and 105 blood bank donors were studied by the pIgM-RF ELISA. Increased levels of cIC were demonstrated in 41.4% of the SLE group, in 8.2% of the breast cancer group, and in 1.9% of the normal control group. The difference in cIC activity between the SLE group and the normal control group was statistically significant.
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PMID:A polyclonal IgM-RF enzyme-linked immunosorbent assay for the detection of circulating immune complexes. 319 29

Three different tests which are based on different principles were used for the detection of soluble immune complexes (IC): (i) a PEG precipitation test, which is based on the solubility characteristics of IC; (ii) a solid-phase C1q binding assay, which is based on the complement binding property of IC, and uses peroxidase-linked anti-human IgG to detect the bound IC (C1q-ELISA); and (iii) the indirect granulocyte phagocytosis test (IGPT) which is based on the Fc R- and possibly the C3 R-binding of IC. Using heat-aggregated IgG (A-IgG) as a model for soluble IC all three tests showed a linear relation with the amount of A-IgG. The C1q-ELISA and the IGPT had a detection limit of less than 1 microgram/ml while the PEG test only detected quantities of more than 10 micrograms/ml. However, when using artificially produced soluble IC, which were prepared from human antibodies (ab) of different specificities and their respective antigens (ag) i.e., (i) tetanus toxoid, (ii) Helix pomatia hemocyanin (HPH), and (iii) dsDNA, and which consisted of the two components in a wide range of ag/ab ratios, distinct results were obtained with the three tests. Thus demonstrating that results obtained with A-IgG as a model for soluble IC can not simply be extrapolated to the behavior of real complexes in IC detection assays. No matter which ag was used, the composition of the IC, i.e., the ratio in which ag and ab were present, appeared to be the crucial factor for detectability in the different tests. The C1q-ELISA can detect IC over a wide range of ag/ab ratios, while it is particularly sensitive for IC formed in slight ag excess. The IGPT in contrast primarily detects, and is highly sensitive for, IC formed in ab excess. The PEG test appears to detect IC with freshly bound complement only. Another interesting finding has to be mentioned here: when increasing amounts of dsDNA were added to a SLE serum containing anti-DNA ab, the IC that had been detectable in the native serum with the IGPT completely disappeared, thus demonstrating that these complexes did consist of DNA and anti-DNA.
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PMID:Characterization of the soluble immune complexes that are detected by three different techniques. 348 41


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