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 effect of 23 antiphospholipid antibody positive SLE sera, 4 antiphospholipid antibody negative SLE sera and 17 control sera on endothelial prostacyclin and platelet thromboxane A2 production was studied. Endothelial cells and platelets were stimulated with different agonists. Depending on the stimulus used, 4-19% of the SLE sera inhibited the prostacyclin release, whereas 4-28% enhanced prostacyclin production. Our data suggest that the pathophysiological mechanisms underlying decreased prostacyclin production are heterogeneous. Follow-up of two patients showed that prostacyclin inhibitory activity was variable in time. Platelet thromboxane production was normal or increased, but never decreased in the presence of the SLE sera. An imbalance in thromboxane A2/prostacyclin ratio was present in some patients, but did not correlate with a history of thrombosis. We conclude that, in general, interference of antiphospholipid antibodies with endothelial or platelet prostanoid synthesis does not explain the occurrence of thromboembolic manifestations in antiphospholipid antibody positive SLE patients.
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PMID:Thrombosis associated with antiphospholipid antibodies cannot be explained by effects on endothelial and platelet prostanoid synthesis. 312 12

Lupus anticoagulant is more often associated with thromboembolism than hemorrhage. We have observed two cases of lupus anticoagulant associated with basal ganglion lacunar infarction, causing contralateral choreoathetosis. One patient had no evidence of lupus or other etiology, and responded to antiplatelet therapy, while the other was found to have systemic lupus erythematosus with nephritis and was successfully treated with steroids. The effects of lupus anticoagulant on platelet prostacyclin receptors or prostacyclin production, or its effect on cerebral vessels may permit small-vessel occlusion and lacunar infarction in susceptible patients.
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PMID:Lupus anticoagulant and lacunar infarctions. 313 15

Decreased endothelial cell production of prostacyclin (PGI2) in response to the lupus anticoagulant has been previously demonstrated and postulated to have a causal relationship to the thrombotic events associated with the lupus anticoagulant. Five patients who exhibited the anticoagulant were studied in an effort to determine if a relationship exists between exposure of endothelial cells to the lupus anticoagulant and decreased production of PGI2. Human endothelial cells derived from human umbilical vein grown in culture were exposed to IgG fractions of patient plasmas containing the lupus anticoagulant. PGI2 released per 10(6) cells was determined by radioimmunoassay for 6-keto-PGF-1-alpha. The overall means for the patient and control groups are given by 47 pM/10(6) cells and 12 pM/10(6) cells respectively. This is a statistically significant difference (F = 10.65, p = 0.017) when the effects of different batches of endothelial cells and thrombin stimulation are adjusted for in the analysis of variance model. These results demonstrate that in this homologous human system exposure of endothelial cells to the lupus anticoagulant leads to stimulation rather than inhibition of PGI2 release.
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PMID:The lupus anticoagulant stimulates the release of prostacyclin from human endothelial cells. 313 89

Defective plasmatic stimulation of prostacyclin (PGI2) production by vascular cells has been described in patients with lupus anticoagulant (LAC). A young woman with recurrent abortions, LAC and evidence for deficient PGI2 production was studied. Serial measurements of a plasma PGI2 inhibitor, LAC and anticardiolipin antibodies (ACA) have been performed before and throughout her fourth pregnancy. Antenatal care and treatment with prednisone and heparin started at 10 weeks gestation. The plasma of our patient continued to inhibit PGI2 production by vascular cells despite treatment. The presence of inhibitor(s) of PGI2 release was confirmed by mixing the patient's plasma with normal plasma. In addition, an IgM lupus anticoagulant fraction (but not the IgG fraction) interfered with the release of arachidonic acid in human endothelial cells induced by thrombin. Despite prednisone and heparin treatment we did not find a complete correction of the LAC activity and the ACA (IgM type) still remained positive before the detection of a fetal death at 26 weeks. The placenta showed abundant infarcts and areas of ischaemic necrosis. We suggest that the defect in vascular PGI2 release could compromise fetal outcome.
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PMID:Serial measurements of a plasma prostacyclin inhibitor in a patient with recurrent abortions and lupus anticoagulant; a case report. 314 99

A case is reported of systemic lupus erythematosus (SLE) associated with steroid-resistant nephrotic syndrome. Serial plasma exchanges (PE) combined with prednisolone treatment induced complete normalization of the immunological findings: the anti-DNA antibody, antinuclear antibody, LE cell phenomenon and circulatory immune complexes became negative. The prostacyclin (PGI2) production-supporting activity in the plasma increased to the control range; inhibitors of PGI2 production were eliminated. The creatinine clearance normalized, the urinary protein excretion decreased significantly, and the facial erythema disappeared. Continued treatment with chlorambucil + low-dose prednisolone led to a complete and stable remission of the nephrotic syndrome, and the C3 complement normalized. The low level of PGI2 production-supporting activity in the plasma may be explained by the inhibitor of PGI2 production. PE + immunosuppressive therapy might have beneficial effects on the immunological changes and PGI2 metabolism, and also on the remission of SLE-nephrotic syndrome.
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PMID:Plasma exchange and immunosuppressive therapy in a paediatric patient with systemic lupus erythematosus. 315 82

Plasma prostacyclin (PGI2) degradation rates were measured at 1, 5, 15 and 30 min in a group of patients with platelet quantitative disorders of various pathogeneses, including 13 with thrombocytosis, 16 with thrombocytopenia from impaired production in the bone marrow, 11 with thrombocytopenia from peripheral destruction, and 28 normal, healthy persons. Patients with thrombocytosis had a low PGI2 degradation rate, whereas patients with thrombocytopenia due to impaired production had a high PGI2 degradation rate. Of the patients with thrombocytopenia caused by peripheral destruction, six with idiopathic thrombocytopenia purpura (ITP) had a slow PGI2 degradation in contrast to five with systemic lupus erythematosus (SLE) - four concurrently had cryoglobulinemia - who had a rapid PGI2 degradation. The findings suggest that: (1) a platelet-derived substance in the human plasma may have a PGI2 stabilising activity; (2) presence of cryoglobulin or immune complex in plasma may interfere with PGI2 stability.
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PMID:Prostacyclin degradation in patients with quantitative platelet disorders. 329 Sep 5

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.
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PMID:Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. 390 Jan 32

Dietary supplementation of fish oil as the exclusive source of lipid suppresses autoimmune lupus in MRL-lpr mice. This marine oil diet decreases the lymphoid hyperplasia regulated by the lpr gene, prevents an increase in macrophage surface Ia expression, reduces the formation of circulating retroviral gp70 immune complexes, delays the onset of renal disease, and prolongs survival. We show that a fatty acid component uniquely present in fish oil but not in vegetable oil decreases the quantity of dienoic prostaglandin E, thromboxane B, and prostacyclin normally synthesized by multiple tissues, including kidney, lung, and macrophages, and promotes the synthesis of small amounts of trienoic prostaglandin in autoimmune mice. We suggest that this change in endogenous cyclooxygenase metabolite synthesis directly suppresses immunologic and/or inflammatory mediators of murine lupus.
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PMID:A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice. 391 11

A 46 year old man with intermittent claudication due to severe peripheral vascular disease had a circulating lupus like anticoagulant (LLAC), thrombocytopenia (79 X 109/1), markedly reduced platelet survival and a normal bone marrow. He was treated with intravenous prostacyclin (PGI2) infusions which resulted in improvement of the patient's exercise tolerance and normalisation of his platelet count (300 X 109/1) and platelet aggregation could then be assessed. The platelets were markedly hyperaggregable and generated supranormal quantities of thromboxane A2. A diagnosis of consumptive thrombocytopenia secondary to peripheral vascular disease and platelet hyperaggregability was made. Despite therapy with aspirin and dipyridamole, gradual and progressive reduction in platelet count followed and his exercise tolerance declined over the next three months. Immunoglobulin prepared from the patient's serum did not inhibit vascular PGI2 synthesis in vitro. To our knowledge this is the first reported case of consumptive thrombocytopenia due to severe peripheral vascular disease and platelet hyperaggregability. PGI2 administration caused a transient resolution of these features which was not sustained by aspirin and dipyridamole.
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PMID:Thrombocytopenia and lupus-like anticoagulant in a patient with peripheral vascular disease: response to infusion of prostacyclin. 392 87

In a 31-year-old woman with a history of recurrent arterial thrombosis, both of whose pregnancies had resulted in intrauterine death at 23 and 24 weeks, a "lupus" anticoagulant was identified. The patient's IgG fraction, containing the lupus anticoagulant, reduced the release of prostacyclin (PGI2) from rat aorta rings or pregnant human myometrium. This inhibitory effect was abolished in the presence of arachidonic acid. The production of 6-keto-PGF1 alpha by cultured bovine endothelial cells was also decreased in the presence of the patient's IgG fraction. The plasma level of 6-keto-PGF1 alpha was reduced. An antibody in this patient may interfere with the production or release of PGI2 by the vessel wall, possibly by interfering with the availability of arachidonic acid. This mechanism could play a role in this patient's arterial disease and obstetric problems.
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PMID:Arterial thrombosis, intrauterine death and "lupus" antiocoagulant: detection of immunoglobulin interfering with prostacyclin formation. 610 1


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