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)

Antiphospholipid antibodies (APA) are a family of immunoglobulins that react with anionic phospholipids, or anionic phospholipids-protein complexes. Recent evidence would support the latter definition. Lupus anticoagulants (LA) inhibit in vitro phospholipid dependent coagulation tests [e.g., activated partial thromboplastin time (APTT), prothrombin time (PT), and dilute Russell viper venom time (dRVVT)]. This inhibition appears to be specific for reagent phospholipids. The addition of freeze-thawed platelets or activated platelets will result in correction of the LA-induced abnormality. Anticardiolipin antibodies (ACA) are related to LA but appear to be distinct. ACA are detected by solid phase assays (ELISA, RIA) and require a plasma cofactor: beta 2 Glycoprotein-I (beta 2 GPI). ACA and LA activities can be separated in individual patient plasmas by affinity chromatography. In some instances they are of differing isotypes. Preliminary evaluation of beta 2 GPI in coagulation assays suggests it may function as a cofactor for LA activity. Recent work also suggests human prothrombin may represent a necessary cofactor for in vitro LA activity. Paradoxically, patients with LA/ACA may sustain thromboembolic events involving both venous and arterial sites. The prothrombotic properties of LA/ACA have not been satisfactorily characterized. A number of proposals have been reported, including inhibition of prostacyclin (PGI2) generation by endothelial cells, decreased activity of the protein C system, impaired fibrinolysis, and inhibition of beta 2GPI. Among these various hypotheses, down regulation of the protein C system appears most plausible. Also, LA/ACA may interfere with the phospholipase A2-phospholipid substrate complex involved in the generation of arachidonic acid from membrane phospholipids.
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PMID:Antiphospholipid antibodies: proposed mechanisms of action. 128 81

The objective of this study was to clarify the specificity of anticardiolipin antibodies (aCL). Eighteen monoclonal hybridoma aCL from systemic lupus erythematosus (SLE)-prone MRL/Mp-lpr/lpr mice were established, and the reactivity of monoclonal aCL to phospholipids, DNA, nuclei of human epithelial cells, platelets, vascular endothelial cells, heparin, protein C and thrombomodulin was examined. All the 18 monoclonal aCL reacted with phosphatidylserine and some showed reactivity to phosphatidylinositol and phosphatidylcholine. Six of 16 monoclonal aCL were demonstrated to have the property of lupus anticoagulant. Monoclonal aCL were classified into three categories, in terms of DNA-binding specificity. Ten of 18 aCL had characteristics of antinuclear antibodies. Six of 11 aCL reacted with platelets. Three of 18 aCL were bound to vascular endothelial cells and to heparin. No monoclonal aCL reacted with protein C or thrombomodulin. Therefore, the conclusion was made that monoclonal aCL from SLE mice showed a polyspecific nature.
Lupus 1992 Aug
PMID:Monoclonal autoantibodies to cardiolipin derived from SLE mice. 130 87

Racial differences in stroke are known to exist with persons in the black race having a higher morbidity, mortality and incidence of stroke compared to whites. We evaluated coagulation factors in black and white stroke patients and compared the results between races. D-dimer was elevated more frequently in blacks than whites to a statistically significant degree. There were non-significant trends for blacks to have a positive lupus anticoagulant, low protein C and protein S, higher platelet factor 4, and hyporesponsive platelets to 10 microM epinephrine. The significance of these findings in understanding racial differences in stroke is discussed.
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PMID:Racial differences in coagulation studies in stroke. 135 61

Most people who experience venous thrombosis have normal hemostasis. Some people have inherited deficiencies of protein C, protein S, and antithrombin iii. They tend to have deep venous thrombosis which increases their risk for pulmonary emboli. Some acquired disorders which predisposes people to thrombosis include defective fibrinolysis which often occurs after surgery or infection, Trousseau's syndrome (excessive coagulant activity linked with adenocarcinoma), and lupus anticoagulant which is an immunoglobulin G or M antibody directed against negatively charged phospholipids. Hormones and probably not a dilution effect reduces free and bound protein S levels during pregnancy. Functional protein S activity is still 40-50% below normal levels 1-3 days after delivery. This decrease appears to protect against bleeding but does have venous thrombosis and pulmonary emboli during pregnancy as side effects. Non-oral-contraceptive (OC) users have greatly higher protein S levels than do OC users (28.6 mcg/ml vs. 24.3 mcg/ml; p.005) which gives more credence to the belief that hormones are responsible for the fall in protein S activity during pregnancy. OCs reduce free and total protein S levels almost 20%. Smoking may even further reduce these levels in women during pregnancy and who use Ocs. Women who have had venous thrombosis should not use OCs. Physicians should also consider family history especially age of affected family member, severity of thrombotic episodes, and the clinical setting. They should look for an underlying abnormality in patients who develop thrombosis while using OCs. If thrombosis develops during pregnancy, physicians should call for a venogram, venous duplex scanning, and, if required, invasive tests. The most sensible treatment is intravenous heparin for 5-7 days then therapeutic doses of heparin. Heparin therapy should stop before delivery and be reinstituted shortly thereafter and continued throughout the postpartum period. Physicians should take extra precautions when performing surgery on an OC user.
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PMID:Recent advances in understanding clotting and evaluating patients with recurrent thrombosis. 141 44

We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, C15, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and anti-OVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CD5, and TCR-alpha/beta. Three of the seven clones used TCR-V beta 4. However, the V beta expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-gamma. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.
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PMID:Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. 146 Feb 94

We studied the natural inhibitors (NI) of blood coagulation and fibrinolysis in 50 patients with lupus anticoagulant (LA), in order to identify possible alterations of these NI, that could favour thrombotic manifestations. We found no statistically significant difference in antithrombin III, protein C and alpha 2-antiplasmin between controls and patients with LA, irrespective of their clinical manifestations. We found an increase of plasminogen activator inhibitor (PAI, P < 0.001) and a decrease of free protein S (PSf, P < 0.001) and total protein S (PSt, 0.01 < P < 0.05) in the patients with LA when compared with the control group. We found no difference in the levels of NI between patients with thrombosis (n = 19) and without thrombosis (n = 31) nor between patients with (n = 25) or without thrombosis and/or foetal loss (n = 25). In contrast, we observed a decrease of PSf in women with foetal loss (n = 10) as compared with women without foetal loss (n = 22, 0.01 < P < 0.05) and a decrease of PSf when comparing 19 patients with systemic lupus erythematosus (SLE) with 31 patients without SLE (0.01 < P < 0.05). These findings show that the patients with LA had several abnormalities in the NI system, but there was no significant association between levels of PAI, PSf, PSt and a history of thrombosis.
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PMID:Natural inhibitors of blood coagulation and fibrinolysis in patients with lupus anticoagulant. 148 97

Previous studies of patients with thromboembolic disease have revealed an association either with hereditary anticoagulant protein deficiencies or with defects in the fibrinolytic system. To obtain a more comprehensive picture and to investigate which analyses are useful in the evaluation of such patients, we have performed an extensive laboratory investigation in 439 individuals with thromboembolic disease. Anticoagulant protein deficiencies were found in 24 patients. Deficiencies of protein C (n = 10) and protein S (n = 9) were most common followed by deficiencies of antithrombin III (n = 3) and plasminogen (n = 2). Six of the nine protein S deficient patients demonstrated a selective deficiency of free protein S with normal total protein S concentrations. To diagnose protein C and S deficiencies among the 201 patients receiving oral vitamin K antagonists, the concentrations of protein C and S were compared with the mean concentration of several other vitamin K-dependent proteins. One protein C and three protein S deficiencies were identified among the treated patients. The number of protein C deficiencies found in this group was significantly lower than the number found among untreated patients. Although fewer protein S deficiencies were also identified among the treated patients, than in the untreated group, the difference was not statistically significant. The results suggest that protein C deficiencies went undetected in the treated group and that oral anticoagulant therapy should be discontinued before efforts to diagnose protein C deficiency are made. We found no cases with heparin cofactor II deficiency. Lupus anticoagulant was present in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thromboembolic disease--critical evaluation of laboratory investigation. 832 78

We examined the relationship between free protein S deficiency and cerebrovascular disease by reviewing the records of all patients with the diagnoses of cerebral thrombosis, cerebral embolism, and cerebral vascular occlusion who were referred for coagulation studies over a 12-month period. We assayed for free protein S antigen, protein C antigen, and antithrombin III and tested for lupus-like anticoagulant and anticardiolipin antibody. Twenty-two of 267 patients (8.2%) admitted with thrombotic strokes were referred for coagulation studies. Free protein S antigen was significantly lower in women than in men (62 +/- 25% versus 88 +/- 24%, p = 0.03; n = 11 in each group). Six women had free protein S antigen levels below the range recorded for a contemporary group of 24 age-matched normal women (17 to 59% versus 70 to 102%, p less than 0.001); four of these women had cerebral arterial thrombosis and two had venous dural sinus thrombosis. The six women were aged 29 to 55 at the time of their first strokes; two had family members with protein S deficiency, and one of these had died of a stroke at age 52. Other abnormalities in this population included a positive test for lupus-like anticoagulant or anticardiolipin in five patients, a modest decrease in protein S in two men, and one patient with an isolated deficiency of antithrombin III. We conclude that protein S deficiency may be an important risk factor for stroke in middle-aged women but this requires confirmation by prospective studies in unselected patients.
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PMID:Protein S deficiency in middle-aged women with stroke. 153 5

Protein C (PC) and protein S (PS) are components of a potent, natural anticoagulant system. A deficiency of one of these two inhibitors is associated with thrombotic events in young people. A significant reduction in functional PS activity has been observed during normal pregnancy, and recurrent fetal loss may occur in women with lupus anticoagulant (LA) inhibitor. We measured functional PS activity and free PS antigen in 16 non pregnant patients with LA inhibitor and in 17 normal women as controls. A significant difference was observed between patients and controls in functional PS activity (65 +/- 23% vs 87 +/- 15%, p = 0.02) but not in free PS antigen (88 +/- 17% vs 93 +/- 17%). Functional PS activity decreased only in six patients (37%). Removal of IgG from plasma reduced the difference in functional PS activity between patients and controls. Immunologic IgG levels did not correlate with anti-phospholipid antibodies (APA) activities, activated partial thromboplastin time/kaolin clotting time (aPTT/KCT) data or functional PS activity.
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PMID:Functional protein S in women with lupus anticoagulant inhibitor. 153 34

An inherited deficiency of protein C, a recognized hypercoagulable state, may cause a clinically significant deep venous thrombosis. Only some persons with a deficiency of protein C experience thrombosis, and almost always the thrombotic event occurs in the venous circulation. Warfarin-induced skin necrosis, a rare event observed in some patients soon after treatment with warfarin is begun, is believed to be another manifestation of this deficiency. We describe a young woman whose basal functional and antigenic levels of protein C were about 45% and who experienced both deep venous thrombosis and warfarin-induced skin necrosis in a clinically severe course. Evidence for lupus anticoagulants was present, with prolonged activated partial thromboplastin time that was corrected when lysed platelets were added, prolonged Russell's viper venom time, anticardiolipin antibodies, and other laboratory evidence. Lupus anticoagulants are associated also with a significant incidence of thrombosis, including arterial thrombosis, and this patient developed concurrently arterial thrombosis. The combined effects of protein C deficiency and lupus anticoagulants, exacerbated by other potentially thrombogenic conditions, are believed responsible for the severe thrombotic events experienced by this patient.
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PMID:Concurrent protein C deficiency and lupus anticoagulants. 156 44


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