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 patient with systemic lupus erythematosus had severe hypertension, rapidly worsening renal failure, and multiple successive thrombotic cerebrovascular and retinal lesions develop. In a kidney biopsy specimen luminal thrombi were demonstrated in arteries and arterioles, without vasculitic or inflammatory changes. The patient's plasma was markedly deficient in both prostacyclin stimulating factor (PSF) and vascular plasminogen activator (VPA), and also contained a potent inhibitor of in vitro urokinase-induced fibrinolysis. Treatment with ancrod resulted in striking reversal of the progressive renal damage and clinical recovery from the thrombotic cerebrovascular and retinal lesions. This clinical improvement was associated with improved renal histologic appearance, correction of the PSF and VPA deficiencies, and disappearance of the urokinase inhibitor. Possible mechanisms of action of ancrod are discussed.
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PMID:Ancrod in systemic lupus erythematosus with thrombosis. Clinical and fibrinolysis effects. 622 28

Vasculitis in systemic lupus erythematosus (SLE) is associated with the deposition of IgG and complement in blood vessel walls. However, it is not known whether immune injury to endothelial cells is a part of this process. Therefore, we used a solid phase radioimmunoassay to study the ability of IgG from normal human sera and sera from patients with SLE to bind to endothelial cells. In this assay, cultured human umbilical venous endothelial cells were sequentially incubated with normal or SLE sera, goat anti-human IgG, and 125I-labeled staphylococcal protein A (*SPA). After exposure to normal sera, 2.5 +/- 0.5% (mean +/- SD) of the added *SPA bound to the cells, whereas after exposure to SLE sera 13.8 +/- 7.6% of the added *SPA bound to these cells. This difference in binding was highly significant (P less than 0.001). Binding was partially reduced when SLE sera were preincubated with B-lymphocytes or monocytes, but not after exposure to erythrocytes, platelets, or T lymphocytes. Incubation of endothelial cells with the 7S fraction of SLE sera or with the F(ab')2 fragment of SLE-IgG resulted in the deposition of greater than 80% as much IgG as was deposited on endothelial cells by whole serum. However, since higher molecular weight fractions (greater than 7S) of SLE sera were also active, we tested the capacity of endothelial cells to bind IgG complexes. Endothelial cells bound heat-aggregated IgG (HA-IgG) in a saturable manner at one log concentration below the binding of normal monomeric IgG. Binding of HA-IgG to endothelial cells was markedly enhanced by preincubation with a serum source of complement. Both HA-IgG and SLE-IgG also bound to freshly obtained endothelial cells in suspension, as detected by automated fluorescence flow cytometry. Binding of SLE-IgG and HA-IgG to endothelium initiated complement activation, deposition of the third component of complement, and disruption of the monolayer. In addition, SLE-IgG and HA-IgG caused endothelial cells to secrete prostacyclin and caused the adherence of platelets, confirmed by scanning electron microscopy. These studies demonstrate that IgG anti-endothelial antibodies are present in the sera of patients with active SLE. These sera may also contain IgG complexes that are capable of binding to endothelial cells. The association of IgG and complement with endothelial cells may initiate vascular injury in SLE and other human disorders.
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PMID:Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. 636 83

Hypercoagulability may contribute to stroke in young adults. Lupus anticoagulants (LA) were identified in six patients (4%) of 145 young adults with cerebral infarction. The clinical features of the 6 patients in this survey plus an additional patient from another institution with LA-associated stroke are presented. Four had systemic lupus erythematosus and 3 had idiopathic LA; all had mild thrombocytopenia. In 2 patients, no other conditions associated with stroke were discovered after thorough evaluation. Recurrent arterial thrombosis occurred in 4 of 7 patients during an average of two years of follow-up. Evidence suggests that inhibition of prostacyclin formation may occur with LA, promoting a prothrombotic state.
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PMID:Cerebral infarction associated with lupus anticoagulants--preliminary report. 642 Sep 43

Six women, aged 16 to 27 years old at the beginning of their illness suffered recurrent spontaneous abortion (two to eight episodes) and three of them had arteriolar venous thrombosis. These symptoms led to the finding of an antiprothrombinase type of circulating anticoagulant. In two cases, positive dissociated syphilitic serology was observed and all patients presented other haematological abnormalities: thrombocytopaenia and/or autoimmune haemolysis. The diagnosis of disseminated lupus erythematosis was established after an average period of 11 years (range 1 to 27 years) based on at least 4 of the ARA criteria (five out of six cases) and/or characteristic immunological abnormalities (five out of six cases). Thrombosis is more common in lupus when there are associated haematological abnormalities. It is probably directly related to the presence of circulating anticoagulant which inhibits the production and/or secretion of prostacyclin by the endothelial cells.
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PMID:[Recurrent abortions and circulating anticoagulant. Relation to lupic disease: 6 cases]. 651 21

We have investigated the effects of plasma and serum from normal subjects on the production of prostacyclin (PGI2) by cultured porcine aortic vascular endothelial cells, measured by radioimmunoassay of its stable metabolite 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha). Both plasma and serum caused significant stimulation of the production of 6-keto PGF1 alpha over basal levels. Serum caused consistently greater stimulation than plasma from the same individual. Washed platelet suspensions were induced to aggregate using thrombin and the supernatants stimulated the production of 6-keto PGF1 alpha by cultured endothelial cells. Preliminary studies also show that a stimulatory factor is released from cultured human leucocytes. Serum from patients with systemic lupus erythematosus (SLE) and severe systemic sclerosis (SS), two connective tissue diseases with autoimmune features and vascular complications, showed significantly reduced levels of stimulation when compared with a control group.
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PMID:Stimulation of prostacyclin production from vascular endothelial cells by plasma, serum and platelets under normal and pathological conditions. 675 53

Evidence exists of an association between the presence of a "lupus" anticoagulant in plasma, recurrent fetal loss, and repeated thromboembolic accidents, also in the absence of systemic lupus erythematosus. Presented is an example of this association, with morphologic and biologic studies to elucidate its pathogenesis. In the case reported, the placenta showed massive infarction. In the spiral arteries of the basal plate of the placenta, lesions of intimal thickening, fibrinoid necrosis, acute atherosis, and intraluminal thrombosis were observed. The plasma of the patient contained a lupus anticoagulant and inhibited the formation of prostacyclin by rat aortic rings. Vascular production of prostacyclin is a major natural defense mechanism against thrombosis. Lack of generation of prostacyclin may account for the decidual vasculopathy and consequent placental infarction and for the generalized thrombotic tendency of some patients with lupus anticoagulant.
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PMID:Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. 680 84

A "lupus" anticoagulant was discovered in 14 patients over a one year period. Only three of them had systemic lupus erythematosus. Bleeding manifestations were only present in one patient with concomitant severe thrombocytopenia. In contrast, eight patients had a history of thrombosis; five of them presented repeated thrombotic episodes. Obstetrical complications (recurrent abortion, fetal death, or intrauterine growth retardation) were observed in six patients. An inhibitory effect of plasma on the production of prostacyclin by vascular tissue was detected in eight patients, six of whom had thrombosis. We suggest that inhibition of prostacyclin formation could play a major role in the pathogenesis of thrombosis and obstetrical problems in some patients with this type of anticoagulant, even in the absence of systemic lupus erythematosus.
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PMID:"Lupus" anticoagulant and thrombosis--possible role of inhibition of prostacyclin formation. 681 93

We report the observations of 4 young women suffering from SLE witha circulatig antiprothrombinase anticoagulant. Antiprothrombinase is the most frequent circulating anticoagulant found in SLE (5 to 10 p. 100). SLE is the main aetiology for antiprothrombinase (over 50 p. 100). It is called 'lupus anticoagulant'. Some symptoms seem to be more frequent in SLE with antiprothrombinase. Such are biological signs (false positive tests for syphilis. Coombs test, thrombopenia, prothrombin deficiency) and clinical signs (venous or arterial thrombosis particularly if oestroprogestative treatment is taken, bleeding if thrombocytopenia or deficiency of prothrombin; repetitive abortion and may be neuropsychiatric signs). Antiprothrombinase is an autoantibody (IgG or IgG + M) polyclonal in SLE, with antiphospholipid activity. It could decrease the production of prostacyclin (PGI2) from free arachidonic acid derived from membrane bound phospholipids. Immunological properties of antiprothrombinase could account for clinical and biological associated signs.
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PMID:[Antiprothrombinase type of circulating anticoagulants during acute disseminated lupus erythematosus]. 698 16

When fresh rabbit aorta is incubated with plasma, prostacyclin, a potent inhibitor of platelet aggregation, is normally released. Plasma obtained from 2 patients with systemic lupus erythematosus (SLE) inhibited prostacyclin activity, while plasma from 22 other patients with SLE and 40 normal control subjects showed normal activity. Absence of prostacyclin activity did not appear to correlate with the clinical severity of the underlying disease. The possible association of this finding and the presence of thrombotic lesions in both patients is discussed.
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PMID:Reduced prostacyclin activity in systemic lupus erythematosus. 700 67

Two classes of antiphospholipid antibodies (APA) are associated with adverse pregnancy outcomes. Those APA identified by immunoassays using phospholipid-coated surfaces (e.g., anticardiolipin antibodies) seem to bind to the 57 kD anticoagulant protein, beta 2-glycoprotein-I, when complexed with anionic phospholipid bilayers. Such APA may or may not prolong phospholipid-dependent clotting assays. A second class of APA are identified by their interference with phospholipid-dependent clotting assays (i.e., lupus anticoagulants). The latter bind to phospholipids present in a unique hexagonal phase either alone or complexed with prothrombin or beta 2-glycoprotein-I. There is evidence that both classes of APA are directly responsible for adverse pregnancy outcomes including spontaneous abortions, stillbirths, fetal growth retardation, thrombosis, thrombocytopenia, and preeclampsia. Putative APA-mediated pathogenic mechanisms include intervillous thrombosis, intravillous infarctions and decidual vasculopathy. The thrombogenicity of APA may result from their interference with endothelial phospholipids required for antithrombin III and protein C and S anticoagulant activity and prostacyclin synthesis and/or increased endothelial expression of the procoagulants: tissue factor, von Willebrand factor, platelet-activating factor, and plasminogen activator inhibitor type-1. Other prothrombotic properties seem to include: increased platelet aggregation, and reduced beta 2-glycoprotein-1 and annexin V anticoagulant activity. Rigorous diagnostic criteria must be applied to the detection of both classes of APA because the prevention of adverse pregnancy outcomes requires potentially hazardous anticoagulant therapy.
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PMID:The immunobiology and obstetrical consequences of antiphospholipid antibodies. 752 11


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