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)

The antibody to cardiolipin(ACA) was tested in patients with systemic rheumatic disease. The frequency of IgG ACA was 46/100(46.0%) in systemic lupus erythematosus(SLE). In other rheumatic disease, this was less than 20%. Significant correlation between the presence of IgG ACA and thrombosis and/or thrombocytopenia was found in patients with SLE. Eight sera containing high titered IgG ACA from lupus patients were selected for further inhibition study. Inhibitors were consisted of cardiolipin(CL), phosphatidyl(p-)serine, p-inositol, p-glycerol, p-ethanolamine, p-choline, ds-DNA, ss-DNA, fresh platelets(PLT)and fresh red blood cells(RBC). All sera were markedly inhibited by negatively charged phospholipids. In 4 sera(group B), there was moderate inhibition by ss-DNA, ds-DNA, PLT and RBC. In another 4 sera(group A), mild but significant inhibition was obtained by PLT alone. The number of platelet in group A was less than that in group B. There were some differences in inhibitory activity, suggesting heterogeneity of antibody to CL. It may be possible to speculate that heterogeneity of IgG ACA cause various combination of clinical features such as thrombocytopenia and thrombosis.
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PMID:[Heterogeneity of anticardiolipin antibody]. 192 93

In a search for specific binding patterns of anti-phospholipid (PL) antibody reactivity in sera from patients with systemic lupus erythematosus (SLE), a quantitative assay was used to compare binding curves with those from beef heart cardiolipin (CL) and the following CL analogues: diphosphatidyl propylene glycol (DPPG), which lacks the internal hydroxyl group on the glycerol moiety; acetyl CL (ACL), in which an acetyl group is substituted for the glycerol hydroxyl group; and dimethyl CL (DCL), in which a methyl group is positioned on each phosphate group. In syphilitic sera the plateau level of antibody binding was decreased by 15 and 41% with DPPG and ACL, respectively. Binding to DCL was dramatically suppressed to levels only slightly above baseline. Only the binding curves for CL and DPPG showed saturability, and analysis by Eadie-Scatchard plots showed that the change in binding was primarily due to a more than twofold increase in KD (decreased antibody avidity). Similar patterns were seen with sera from patients with SLE and SLE-like illness, but some uniquely shaped binding curves were observed. Compared to control CL, peak binding levels were 75-88% for DPPG, 16-20% for ACL, and only 1-4% for DCL. These data indicate that the integrity of the CL headgroup, especially at the phosphate moiety, is essential for recognition by anti-CL antibodies from some sources.
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PMID:The structural requirements for anti-cardiolipin antibody binding in sera from patients with syphilis and SLE. 239 Aug 12

U5 small nuclear ribonucleoprotein (snRNP), purified from HeLa nuclear extracts (splicing extracts), shows a complex protein composition. In addition to the snRNP proteins B', B, D, D', E, F, and G, which are present in each of the major snRNPs U1, U2, U4/U6, and U5, U5 snRNP contains a number of unique proteins characterized by apparent molecular masses of 40, 52, 100, 102, 116, and 200 (mostly a double band) kDa. The latter set of proteins may be regarded as U5-specific for the following reasons. They are not only eluted specifically, together with snRNP particles, from anti-2,2,7-trimethylguanosine immunoaffinity columns by 7-methylguanosine, they also cofractionate with U5 snRNP during chromatography and, most importantly, in glycerol gradient centrifugation. These U5 snRNP particles show a high sedimentation constant of about 20S. U5 snRNPs that lack the U5-specific proteins are also found in nuclear extracts but have (in comparison) a lower sedimentation value of only 8-10S. Autoimmune sera from patients with systemic lupus erythematosus were identified that, on immunoblots with purified U5 snRNP proteins, reacted selectively with the 100- or 200-kDa proteins. This indicates that at least the high molecular mass U5-specific proteins are structurally distinct and not derived one from the other by proteolytic degradation. The existence of so many unique proteins in the U5 snRNP suggests that this snRNP particle may exert its function during splicing mainly by virtue of its protein components.
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PMID:20S small nuclear ribonucleoprotein U5 shows a surprisingly complex protein composition. 252 69

A 37-year-old female who suffered from SLE had a bleeding disorder. At the time of initial evaluation, the main disease demonstrated was a delta-storage pool deficiency. After this improved, a marked decrease of aggregation still remained, when induced by either ADP, epinephrine, collagen, A23187, thrombin, or PAF-acether. Although arachidonate-induced aggregation was slightly decreased, thromboxane B2 was produced normally in response to exogenous arachidonate. The patient's endoperoxides and/or thromboxane A2 aggregated aspirin-treated platelets, though her platelets were themselves unresponsive. Impaired aggregability induced by TPA (12-0-tetradecanoylphorbol-13-acetate) or OAG (1-oleoyl-2-acetyl-glycerol) was also found. However, the phosphorylation of P43 and P20 induced by several stimulators including CA++ ionophore was normal, using 32P-labelled platelets. It is suggested that TPA or OAG-induced platelet aggregation requires not only the phosphorylation of those proteins, but also another unknown mechanism after the phosphorylation, and that the platelet dysfunction of this patient was due to a defect of some mechanism involving Ca++ uptake or mobilization of cytoplasmic Ca++ from intracellular storage sites.
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PMID:A defect of platelet release reaction in a patient with SLE: impaired platelet aggregation induced by phorbol ester with a normal phosphorylation of 40K protein. 308 95

Antiphospholipid antibodies have been determined in two groups of 48 sera from patients with systemic lupus erythematosus (SLE) and syphilis. Using an ELISA, IgG anticardiolipin (CL), antiphosphatidyl serine (PS) and antiphosphatidyl ethanolamine (PEA), antibodies have been detected with the same frequency in both groups of patients. Titres of antiphosphatidyl serine (PS) (p less than 0.005) and PEA antibodies (p less than 0.05) were significantly higher in the syphilitic sera compared to the SLE sera. Anticardiolipin binding activity of both groups of sera could be inhibited by preincubation with phosphatidic acid, phosphatidyl serine, phosphatidyl glycerol and cardiolipin antigens, but the inhibiting ratio of phosphatidyl antigen was significantly higher (p less than 0.01) in the SLE group. These data suggest that anticardiolipin auto-antibodies present in SLE sera are very similar to the "reagins" or antibodies to cardiolipin seen in syphilitic sera. IgG anticardiolipin antibodies may be an epiphenomenon and are probably not implicated in the pathogenesis of the thrombotic diathesis seen preferentially in some patients with SLE.
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PMID:Profile and cross-reactivities of antiphospholipid antibodies in systemic lupus erythematosus and syphilis. 312 5

In this study we have attempted to define the cross-reactive potential of SLE anti-DNA antibodies (in 19 representative sera and plasmas) in both the solution phase and the solid phase. We used the Farr and RBC-CF solution phase assays to measure quantitatively the ability of a variety of negatively charged structurally unrelated molecules to inhibit antibody binding to both native DNA (nDNA) and denatured DNA (dDNA). The inhibitors used were of two types: 1) phospholipids (cardiolipin, phosphatidyl glycerol, and phosphatidic acid) and 2) repeating negatively charged molecules (poly-glutamic acid, heparin sulfate, and chondroitin sulfate). We found in both assays that the phospholipids could inhibit antibody binding to nDNA and dDNA, but a large excess (about 1500-fold) of these molecules was needed relative to DNA to achieve equivalent levels of inhibition. The repeating negatively charged molecules did not inhibit DNA binding at equivalent molar levels as the phospholipids; generally, at least a 10,000-fold excess was needed relative to the nucleic acids to achieve any appreciable inhibition. Results of a dDNA binding-inhibition solid-phase ELISA for cross-reactivity of the anti-DNA antibodies gave quite similar results. Finally, we found that eight of the SLE samples did have anti-cardiolipin antibodies, as demonstrated in a cardiolipin-based ELISA. These results suggest that previous reports describing an apparent cross-reactivity of anti-DNA antibodies may not represent physiologically relevant interactions between anti-DNA antibodies and non-nucleic acid antigens.
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PMID:Quantitative aspects of lupus anti-DNA autoantibody specificity. 348 4

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

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

The proliferating cell nuclear Ag (PCNA) is a DNA replication factor postulated to function as a sliding clamp around DNA. PCNA is also a target for autoimmunity in systemic lupus erythematosus. The autoantigenicity of PCNA is highly conformation-dependent, and reaction with most anti-PCNA sera requires a nearly full-length PCNA molecule. Here we describe the use of gel filtration and glycerol gradient sedimentation to analyze the native structure and size of PCNA. PCNA from three sources was studied (PCNA from HeLa cells, PCNA purified after its overexpression in bacteria, and PCNA produced in the wheat germ cell-free translation system) as well as mutant forms of PCNA translated in vitro. In each case, full-length PCNA behaved as a trimer. Analysis of mutant proteins revealed a correlation between the trimeric form and binding to the common type of human anti-PCNA autoantibody, suggesting that the Abs are specific for the active form of the protein. These findings are consistent with the idea that autoantibodies are generated as a response to native Ag and provide experimental support for the hypothesis that PCNA serves its processive function in DNA replication as a trimeric ring structure.
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PMID:Trimeric structure of human proliferating cell nuclear antigen. Implications for enzymatic function and autoantibody recognition. 752 48

An acyl spin-label derivative of 5-aminoeosin (5-SLE) was chemically synthesized and employed in studies of rotational dynamics of the free probe and of the probe when bound noncovalently to bovine serum albumin using the spectroscopic techniques of fluorescence anisotropy decay and electron paramagnetic resonance (EPR) and their long-lifetime counterparts phosphorescence anisotropy decay and saturation transfer EPR. Previous work (Beth, A. H., Cobb, C. E., and J. M. Beechem, 1992. Synthesis and characterization of a combined fluorescence, phosphorescence, and electron paramagnetic resonance probe. Society of Photo-Optical Instrumentation Engineers. Time-Resolved Laser Spectroscopy III. 504-512) has shown that the spin-label moiety only slightly altered the fluorescence and phosphorescence lifetimes and quantum yields of 5-SLE when compared with 5-SLE whose nitroxide had been reduced with ascorbate and with the diamagnetic homolog 5-acetyleosin. In the present work, we have utilized time-resolved fluorescence anisotropy decay and linear EPR spectroscopies to observe and quantitate the psec motions of 5-SLE in solution and the nsec motions of the 5-SLE-bovine serum albumin complex. Time-resolved phosphorescence anisotropy decay and saturation transfer EPR studies have been carried out to observe and quantitate the microseconds motions of the 5-SLE-albumin complex in glycerol/buffer solutions of varying viscosity. These latter studies have enabled a rigorous comparison of rotational correlation times obtained from these complementary techniques to be made with a single probe. The studies described demonstrate that it is possible to employ a single molecular probe to carry out the full range of fluorescence, phosphorescence, EPR, and saturation transfer EPR studies. It is anticipated that "dual" molecular probes of this general type will significantly enhance capabilities for extracting dynamics and structural information from macromolecules and their functional assemblies.
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PMID:Protein rotational dynamics investigated with a dual EPR/optical molecular probe. Spin-labeled eosin. 768 51


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