Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted this study to determine whether antiprothrombin antibody (aPT) [to prothrombin (PT) alone or PT/phosphatidyl serine (PS) complex] actually existed in patients with lupus anticoagulant (LA) and/or anticardiolipin antibody (aCL). aPT to PT alone was positive in 2/7 LA-positive (29%) and 3/7 LA/aCL-positive (43%) patients. aPT to PT/PS complex was positive in 4/7 LA-positive (57%) and 4/7 LA/aCL-positive (57%) patients in the presence of Ca2+. However, none of the aCL-positive patients without LA or the LA/aCL-negative patients were positive for aPT and aPT/PS. Thus, we confirmed the existence of aPT and aPT/PS specifically among LA-positive patients. However, the clinicopathological significance of aPT and aPT/PS in this clinical setting is yet to be clarified.
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PMID:Phosphatidyl serine-dependent antiprothrombin antibody is exclusive to patients with lupus anticoagulant. 867 May 83

In studies of patients in Norway with multiple sclerosis (MS), we have found cross reactive autoantibodies related to the Epstein Barr virus nuclear antigen-1 (EBNA-1). The MS patients had elevated IgG antibody to EBNA-1, as measured by reactivity with a synthetic glycine/alanine peptide, P62, which represents the glycine/alanine repeat in EBNA-1. The mean titer of anti-P62 in patients with acute relapse at the time of assay was significantly higher than in the remaining patients. Patients with remitting/relapsing MS also had elevated autoantibody to a lymphocyte protein, p542, cross reactive with EBNA-1 through a glycine/serine epitope. High titered anti-EBNA-1 antibodies from some MS, as well as from some SLE sera, were shown to cross react with 80-82 kDa and 60 kDa proteins in neuroglial cells.
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PMID:An Epstein Barr virus-related cross reactive autoimmune response in multiple sclerosis in Norway. 882 80

C1-inhibitor (C1-Inh) is a serine esterase proteinase inhibitor (serpin) which plays an important role in regulating serine proteinases of the early inflammatory response. In this study, we describe a novel and versatile polyclonal antibody capture assay to examine C1-Inh consumption in vivo. This assay has advantages over previously described methods of measuring C1-Inh consumption as it allows the assessment of the relative amounts of native, complexed and cleaved inhibitor circulating in plasma. By using polyclonal antibodies specific for other complement proteins, the C1-Inh capture assay was adapted to measure in vivo activation of C3, C4 and factor B. C1-Inh consumption and complement activation were examined in the plasma of 21 normal individuals, 24 individuals with systemic lupus erythematosus (SLE), nine individuals with adult respiratory distress syndrome (ARDS) and in the paired plasma and synovial fluid from 18 patients with rheumatoid arthritis (RA). The C1-Inh capture assay revealed native, cleaved and complexed C1-Inh migrating at 115 kDa, 96 kDa and 209-225 kDa respectively, in normal plasma. C1-Inh consumption was increased in the plasma of all the inflammatory disorders examined, in comparison to normal plasma. It is proposed that this serpin capture assay could be adapted to the study of serpin involvement in a wide variety of inflammatory disorders.
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PMID:A solid-phase antibody capture assay for the measurement of C1-inhibitor consumption in vivo. 885 Jan 66

Preliminary evidence suggests there is a toxin in the sera of systemic lupus erythematosus patients which reacts with a commercial enzyme-linked immunosorbent assay kit for the detection of the marine toxin, okadaic acid. Data is presented which supports the hypothesis that an okadaic acid-like toxin may be the principle agent of lymphocyte dysregulation in systemic lupus erythematosus and other immune-dysregulated states. The okadaic acid-like toxin can produce the specific abnormalities in T-lymphocyte phenotype and function typical of systemic lupus erythematosus, principally through its ability to inhibit serine/threonine phosphatases necessary for secondary signalling processes and through its ability to inhibit calcium which is crucial to protein kinase C-mediated signalling of T-lymphocytes. The disruption probably occurs through the protein tyrosine kinase p56lck pathway crucial for IL-2. Additionally, the toxin's ability to disrupt voltage-sensitive ion channels in cell membranes may be responsible for the multi-organ pathology observed in systemic lupus erythematosus patients, particularly neurological, cardiac and nephritic. Data from a different study conducted by the author suggests that latent and persistent viruses are reactivated in active lupus. This activation could be the result of the toxin's ability to act as an immune modulator, or its ability to act as a transactivating factor.
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PMID:Okadaic acid-like toxin in systemic lupus erythematosus patients: hypothesis for toxin-induced pathology, immune dysregulation, and transactivation of herpesviruses. 889 23

Proteins cleaved by interleukin-1 beta converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated in cells undergoing apoptosis are also targets for autoantibody production in patients with autoimmune disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrome), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irradiation, ultraviolet irradiation), but not with an activation (i.e., CD3-ligation) stimulus. Sera derived from individual patients precipitated different combinations of seven distinct serine-phosphorylated proteins. None of these phosphoproteins were included in precipitates prepared using sera from patients with diseases that are not associated with autoantibody production or using serum from rheumatoid arthritis patients. Protein phosphorylation precedes, or is coincident with, the induction of DNA fragmentation, and is not observed when apoptosis is inhibited by overexpression of bcl-2. Serum from four patients precipitated a serine/threonine kinase from apoptotic cell lysates that phosphorylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. Our results suggest that proteins phosphorylated during apoptosis may be preferred targets for autoantibody production in patients with SLE.
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PMID:Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. 912 Mar 90

The authors investigated antiphospholipid antibodies (APA) against phosphatidic acid, ph-ethanolamine, ph-DL-glycerol, ph-inositol, ph-L-serine and cardiolipine in isotypes IgG and IgM in various diagnoses associated with reproduction. They found that the most varied pattern of high levels of these antibodies is in particular in patients with the diagnosis of intractable infertility (in 26.5% women IgG against cardiolipine, in 24.5% patients IgG against ph-inositol and ph-DL-glycerol, in 17.6% women IgG against ph-ethanolamine, in 20.6% women IgG against phosphatidic acid antigens). Intractable infertility, repeated failures of IVF and patients with a basic autoaggressive disease were followed up and their antiphospholipid antibodies were assessed. In one patient follow up of APA revealed SLE before the patient developed clinical symptoms of the disease.
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PMID:[Profile of antiphospholipid antibodies in various diagnoses associated with reproduction]. 941 Apr 25

Proteins subject to proteolysis or phosphorylation during apoptosis are commonly precipitated by autoantibodies found in the serum of patients with systemic lupus erythematosus (SLE). We screened a panel of murine monoclonal and human monospecific sera reactive with known autoantigens for their ability to selectively precipitate phosphoproteins from apoptotic Jurkat T cell lysates. Sera known to recognize the U1-small nuclear ribonucleoprotein (snRNP) complex (confirmed by their ability to precipitate U1-snRNA) selectively precipitated a phosphoprotein complex (pp54, pp42, pp34, and pp23) from apoptotic lysates. Monoclonal antibodies reactive with U1-snRNP proteins precipitated the same phosphoprotein complex from apoptotic lysates. The phosphorylation and/or recruitment of these proteins to the U1-snRNP complex is induced by multiple apoptotic stimuli (e.g., Fas ligation, gamma irradiation, or UV irradiation), and is blocked by overexpression of bcl-2. The U1-snRNP-associated phosphoprotein complex is immunoprecipitated by monoclonal antibodies reactive with serine/arginine (SR) proteins that comprise a structurally related family of splicing factors. The association of phosphorylated SR proteins with the U1-snRNP complex in cells undergoing apoptosis suggests a mechanism for regulation of alternative splicing of apoptotic effector molecules.
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PMID:Association of phosphorylated serine/arginine (SR) splicing factors with the U1-small ribonucleoprotein (snRNP) autoantigen complex accompanies apoptotic cell death. 946 5

Proteins cleaved by apoptotic caspases are commonly recognized by autoantibodies found in the serum of patients with rheumatic disease. We report that the 72-kDa signal recognition particle (SRP) protein, a rare target of autoantibodies found in the serum of patients with dermatomyositis and systemic lupus erythematosus, is rapidly cleaved in Jurkat T cells treated with apoptotic (i.e. Fas ligation, treatment with gamma or ultraviolet radiation, or co-culture with anisomycin or staurosporine) but not proliferative (CD3 cross-linking) stimuli. Cleavage of SRP 72 produces a 66-kDa amino-terminal fragment and a 6-kDa carboxyl-terminal fragment that is selectively phosphorylated on serine residues. Cleavage of SRP 72 is prevented by chemical and peptide caspase inhibitors, and by overexpression of bcl-2, an inhibitor of apoptotic cell death. Analysis of the carboxyl terminus of SRP 72 has identified a putative cleavage site (SELD/A) for group III caspases, and carboxyl-terminal serine residues that are highly conserved in phylogeny. Both serine phosphorylation and caspase cleavage of SRP 72 are observed in cells derived from human, dog, rat, and mouse. Canine SRP 72 is cleaved in vitro by recombinant caspase 3 but retains the ability to mediate transport of a signal peptide-containing protein into the endoplasmic reticulum lumen. The 72-kDa component of the SRP joins a growing list of autoantigens that undergo post-translational modifications during programmed cell death.
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PMID:The 72-kDa component of signal recognition particle is cleaved during apoptosis. 985 79

Increased prevalence of anti-phospholipid antibodies (aPL) and increased levels of lipid peroxidation have been described in patients with HIV infection. To assess the binding specificity and avidity of aPL antibodies in HIV infection, sera from 44 HIV-1 infected patients were evaluated for antibodies to cardiolipin (aCL), phosphatidyl serine (aPS), phosphatidyl inositol (aPI) and phosphatidyl choline (aPC) using enzyme linked immunosorbent assay (ELISA) methods. Sera from 30 patients with systemic lupus erythematosus (SLE), but without features of anti-phospholipid syndrome (APS) (SLE/non APS), six with SLE and secondary APS, (SLE/APS) and 11 with primary APS (PAPS) were also evaluated as controls. The resistance of the aPL antibody binding to dissociating agents was evaluated by treating the ELISA wells, after serum incubation with 2 M urea or 0.6 M NaCl for 10 min. An anti-beta2-glycoprotein-I (beta2-GPI) ELISA was used to assess serum reactivity against beta2-GPI, a plasma protein considered as the true antigen of aCL antibodies occurring in APS and SLE patients. The prevalence of aCL, aPS, aPI and aPC antibodies in HIV-1 infection was 36%, 56%, 34% and 43% respectively, which was comparable to that found in SLE/APS and PAPS patients and significantly higher than that observed in SLE/non-APS patients. Anti-beta2-GPI antibodies occurred in 5% of HIV-1 infected vs. 17% in SLE/non-APS (P=0.11), 50% in SLE/APS (P=0.009) and 70% in PAPS patients (P=0.0014). A significant decrease of aPL binding after urea and NaCl treatment was observed in the sera of HIV-1-infected, compared to that of APS patients, indicating that aPL antibodies from HIV-1 infected individuals have low resistance to dissociating agents. In conclusion, aPL antibodies (1) occur in HIV-1 infection; (2) tend to recognize various phospholipids but not beta2-GPI; and (3) are of low resistance to dissociating agents-a finding probably reflecting low antibody avidity. Finally, these, like the autoimmune-type aCL antibodies, tend to recognize the oxidized CL-a finding probably indicating autoantibody generation as a result of neoepitope formation by oxidized PLs.
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PMID:Anti-phospholipid antibodies in HIV infection and SLE with or without anti-phospholipid syndrome: comparisons of phospholipid specificity, avidity and reactivity with beta2-GPI. 1055 Feb 22

Lupus anticoagulants (LA) are a family of autoantibodies that are associated with in vitro anticoagulant activity but a strong predisposition to in vivo thrombosis. They are directed against plasma phospholipid binding proteins, including prothrombin. We found that a murine monoclonal antiprothrombin antibody and 7 of 7 LA IgGs tested enhanced binding of prothrombin to 25:75 phosphatidyl serine:phosphatidyl choline vesicles in a concentration-dependent manner. We hypothesized that enhanced binding of prothrombin to phospholipid in the presence of LA IgG might result in increased thrombin production when reactions are performed in flow. Thrombin production by purified prothrombinase components was measured in a phospholipid-coated flow reactor. The flow reactor was incubated with prothrombin, calcium ions, and the IgGs and then perfused with prothrombin, calcium ions, the IgGs, factor Va, and factor Xa. A murine monoclonal antiprothrombin antibody and 4 of 6 LA IgGs from patients with a history of thrombosis increased thrombin production up to 100% over control in the first 15 minutes. In summary, LA IgGs concentrate prothrombin on a phospholipid surface that can augment thrombin production by prothrombinase in flow. These observations suggest that LA might propagate coagulation in flowing blood by facilitating prothrombin interaction with the damaged blood vessel wall.
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PMID:Lupus anticoagulants form immune complexes with prothrombin and phospholipid that can augment thrombin production in flow. 1055 52


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