Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We observed three patients with lupus erythematosus and porphyria cutanea tarda manifesting itself simultaneously or subsequently. The possible coincidence of the two diseases might be the consequence of immunological communities indicated on the assumption of a genetically coined hepatic uroporphyrinogen decarboxylase defect. The treatment of the lupus erythematosus can be performed according to corresponding observations of the course according to general acknowledged principles including the administration of cytostatic drugs, if the chloroquine phosphate therapy which is clearing up the porphyria cutanea tarda is beginning with low dosages. The fluorescence of the fresh kidney bioptate under long-wave UV-light in porphyria cutanea tarda is referred to for the first time.
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PMID:[Porphyria cutanea tarda and lupus erythematosus]. 258 23

Four murine monoclonal antibodies having high levels of activity against phosphatidyl-inositol phosphate (PIP) were tested for lupus anticoagulant activity. The antibodies showed different degrees of potency in a modified partial thromboplastin time test (APTT) that used dilutions of either bovine brain extract (Thrombofax) or liposomes consisting of phosphatidylcholine/phosphatidylserine (PC/PS) as the phospholipid source. The same relative order of anticoagulant potency that was observed in the APTT that used the PC/PS liposomes was maintained when the anti-PIP antibodies were tested for cross-reactivity either by induction of complement-dependent immune damage to liposomes containing PS, or in enzyme-linked immunosorbent assays that used PS, cardiolipin (CL), or phosphatidylinositol (PI) as antigens. The data indicate that monoclonal antibodies to PIP can express anticoagulant activity in a modified APTT that correlates with their different degrees of cross-reactivity against the negatively-charged phospholipids PS, CL, and PI.
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PMID:Lupus anticoagulant activities of murine monoclonal antibodies to liposomal phosphatidylinositol phosphate. 282 Jun 40

Although observations have implied that lupus anticoagulants have immunologic specificity toward anionic phospholipids, this assumption has been directly demonstrated in only one patient with a monoclonal IgM paraprotein. We tested the generality of this hypothesis directly by isolating five IgG lupus anticoagulants from patients with lupuslike syndromes and/or thrombosis. IgG lupus anticoagulant fractions were isolated free of other plasma proteins and free of contaminating phospholipid by adsorption to and elution from cardiolipin-cholesterol-dicetyl phosphate liposomes, followed by chromatography on protein A-Sepharose. Cardiolipin liposomes, but not phosphatidylcholine liposomes, were capable of removing all, or nearly all, lupus anticoagulant activity from patient plasma. The affinity-purified IgG preparations reacted with cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatidic acid, but not with phosphatidylcholine or phosphatidylethanolamine, and inhibited calcium-dependent binding of prothrombin and of factor X to phosphatidylserine-coated and to cardiolipin-coated surfaces. F(ab')2 fragments retained lupus anticoagulant activity and bound to cardiolipin in an enzyme-linked immunosorbent assay (ELISA). Anticardiolipin and lupus anticoagulant activity were both present in acidic fractions on isoelectric focusing. These data strongly suggest that most, if not all, lupus anticoagulants are antibodies that have immunologic specificity towards anionic phospholipids, thereby blocking the calcium-mediated binding of vitamin K-dependent coagulation factors to coagulation-active phospholipid surfaces.
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PMID:Immunological specificity and mechanism of action of IgG lupus anticoagulants. 310 26

The lupus anticoagulant is usually found in the plasma of patients with systemic lupus erythematosus. Lupus anticoagulants are antibodies to phospholipids and probably to phosphodiester-linked phosphate groups. A high frequency of thrombotic events in patients with lupus anticoagulant has been reported. Nevertheless the pathogenesis of thrombosis in these patients remains unknown. Endothelium which plays a key role in the antithrombogenic-thrombogenic balance could be a target for the lupus anticoagulant and alterations of some endothelial-cell functions could be responsible for the thrombotic events. The effects of the lupus anticoagulant on the phospholipids of the protein C-thrombomodulin complex may be important although evidence of such a reaction in vivo is awaited.
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PMID:The lupus anticoagulant and its role in thrombosis. 313 12

Ratios of activities of oxidative and nonoxidative enzymes involved in the pentose phosphate pathway of carbohydrate metabolism were altered in blood plasma and cells of the patients with systemic impairments of connective tissue. In rheumatoid arthritis and systemic lupus erythematosus the enzymatic activity was increased in blood plasma and cells, while the most distinct activation of the enzymes was found in granulocytes. In systemic sclerodermia total activity of the enzymes involved in metabolism of pentose phosphates in granulocytes exceeded 2.6-fold their values under conditions of normal state, whereas activities of the other enzymes studied remained near normal values. Calculation of ratios (mu value) between activities of the pathway oxidative and nonoxidative enzymes showed that the mu value was increased 2.7-fold in rheumatoid arthritis, while this value was decreased in lupus erythematosus and systemic sclerodermia 4.2- and 2-fold, respectively. The mu values, calculated on the basis of estimation of total activity of dehydrogenases from pentose phosphate pathway and total pentose phosphate metabolizing activity, might serve as a convenient diagnostic criterion for estimation of the ratio between activities of oxidative and nonoxidative enzymes involved in pentose phosphate pathway in granulocytes used for differential diagnosis of systemic impairments of connective tissue (rheumatoid arthritis, lupus erythematosus and systemic sclerodermia).
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PMID:[Pentose phosphate pathway of carbohydrate metabolism in various systemic diseases of the connective tissue]. 323 42

A panel of 65 systemic lupus erythematosus (SLE) and 61 normal-derived human hybridoma auto-antibodies was studied for cytoskeletal reactivity, using an indirect immunofluorescence method. Reactivity with the cytoskeleton was expressed 3 times more frequently in the SLE-derived antibody group and included intermediate filaments, microfilaments, microtubules, and centrioles. By immunoblot analysis, the antigenic specificity of intermediate filament-reactive SLE hybridoma antibodies was not restricted to vimentin, but included cytokeratins and desmin. The antibodies were also studied for their DNA-binding, lupus anticoagulant, and rheumatoid factor activities. These autoantibody activities were expressed 3-5 times more frequently in the SLE-derived group. The ability to bind DNA was not a prerequisite for reactivity with intermediate filament proteins. Our findings suggest that there are at least 2 subsets of cytoskeletal-reactive hybridoma antibodies: those that recognize epitopes found only on cytoskeletal proteins, and those that recognize epitopes common to both DNA and certain cytoskeletal proteins. In addition, we hypothesize that there may be a third subset of antibodies that recognize a phosphate-containing moiety (phospholipid or phosphoprotein) associated with cytoskeletal filaments.
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PMID:Hybridoma lupus autoantibodies can bind major cytoskeletal filaments in the absence of DNA-binding activity. 329 72

Recent studies have raised questions concerning the specificity of anticardiolipin antibodies and their relationship to anti-DNA antibodies, the lupus anticoagulant, the biological false positive test for syphilis, and reagin, the antibody detected in syphilis. In an attempt to answer some of these questions, 3 IgG and 2 IgM affinity purified anticardiolipin antibodies, as well as 3 affinity purified anti-DNA antibodies were studied. Affinity purified anti-cardiolipin antibodies showed high binding to negatively charged phospholipids but not to ssDNA by solid phase radioimmunoassay. On the other hand, affinity purified anti-DNA antibodies did not bind cardiolipin. Inhibition experiments showed that negatively charged phospholipids and VDRL liposomes inhibited the binding of anticardiolipin antibodies to phosphatidylserine, but ssDNA, alpha-glycerol phosphate and hyaluronic acid did not. Similar studies of sera from patients with high anticardiolipin antibody levels supported the results obtained with affinity purified anticardiolipin antibodies. These results suggest that anticardiolipin antibodies bind negatively charged phospholipids and there appears to be little crossreactivity with DNA or unrelated negatively charged polymers such as hyaluronic acid. Both the negatively charged phosphodiester group and glyceride portions of the phospholipid molecules appear important for their antigenicity. Four of the 5 affinity purified anti-cardiolipin antibodies had lupus anticoagulant activity providing further evidence to suggest that these 2 groups of antibodies have the same or very similar specificities. Studies of sera from 3 patients with syphilis showed that VDRL liposomes inhibited reagin activity to a greater extent than did cardiolipin. On the other hand, in patients with autoimmune disorders, cardiolipin inhibited anticardiolipin antibody activity to a greater extent than did VDRL liposomes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Affinity purified anti-cardiolipin and anti-DNA antibodies. 406 29

BALB/c mice immunized with the phospholipid, cardiolipin, produced anti-cardiolipin and anti-DNA antibodies. Seven hybridomas derived from spleen cells of the cardiolipin-immunized mice produced cardiolipin-binding monoclonal antibodies that also bound to the polynucleotides DNA, poly(dT), and poly(I). The seven cardiolipin-induced monoclonal antibodies shared idiotypic determinants with a high frequency idiotypic marker of spontaneously expressed anti-DNA autoantibodies of lupus-prone MRL-lpr/lpr mice. The monoclonal antibodies presumably bound to phosphodiester phosphate groups that occur in both polynucleotides and phospholipids. The results imply that production of anti-DNA autoantibodies does not require immunization by DNA.
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PMID:Monoclonal anti-cardiolipin antibodies bind to DNA. 620 56

Hybridomas the produce anti-DNA autoantibodies were prepared from spleen cells of unimmunized MRL/1 mice, a strain that spontaneously develops severe systemic lupus erythematous (SLE). Reactivities of these monoclonal antibodies with a wide range of polynucleotides prompted tests of their reactions with phospholipids which, like polynucleotides, contain diester-linked phosphate groups in their backbones. In competitive radioimmunoassays, cardiolipin, phosphatidic acid, and phosphatidyl glycerol blocked the binding of these hybridoma antibodies to denatured DNA. These phospholipids also specifically inhibited the reaction between a hybridoma antibody and a site-specific anti-idiotypic antibody. The antinuclear reaction of one of these antibodies was specifically inhibited by cardiolipin. This same antibody prolonged the activated partial thromboplastin time in a manner characteristic of a lupus anticoagulant, presumably by binding to phospholipid in the test system. The polyspecific reactivity of a single molecular species of lupus autoantibody suggests that some of the diverse serological abnormalities of SLE may be a result of the binding of certain autoantibodies to a phosphodiester-containing epitope that is present in diverse biological molecules.
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PMID:Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. 697 93

We studied the TCR/CD3 complex-mediated signal transduction pathway in freshly isolated T cells and T cell lines from patients with systemic lupus erythematosus (SLE). The peak and 5-min anti-CD3 mAb-mediated free intracytoplasmic Ca2+ concentration ([Ca2+]i) increase was statistically significant higher in fresh T cells from SLE patients than in control T cells. Increased CD3-mediated [Ca2+]i responses were observed in T cells from patients with SLE but not in T cells from other rheumatic diseases. Furthermore, significantly increased CD3-mediated [Ca2+]i responses were observed in T cell lines from SLE patients but not from controls. Although the [Ca2+]i response did not correlate with the global SLE disease activity or individual clinical manifestations, it was significantly higher in the group of patients who were not on treatment. Both CD4+ and CD8+ T cell subsets from peripheral blood cells and T cell lines displayed higher CD3-mediated [Ca2+]i responses than their normal counterparts. The peak of the response occurred earlier in the patient than in the normal group. The amount of Ca2+ that was released from the intracellular stores was higher in lupus than control T cells. The TCR/CD3-induced production of inositol phosphate metabolites in SLE cells was comparable with controls. The sarcoplasmic and endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin-induced [Ca2+]i response was similar in both SLE and normal T cells. Our experiments demonstrate for the first time a definite abnormality in the early steps of the TCR/CD3-mediated signal transduction pathway in T cells from SLE patients that involves increased release of Ca2+ from intracellular stores.
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PMID:TCR/CD3 complex-mediated signal transduction pathway in T cells and T cell lines from patients with systemic lupus erythematosus. 763 73


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