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 lupus anticoagulant (LA) positive plasma on the expression of human monocyte procoagulant activity (PCA) was studied. LA positive plasma were able to enhance the endotoxin or TNF alpha induced monocyte associated PCA. The monocyte PCA had the characteristic of tissue factor activity (factor VII, factor X dependence). The enhancement of monocyte PCA could be confirmed using purified LA positive IgG. The stimulating effect was supported by the F(ab')2 fragments.
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PMID:Procoagulant activity of endotoxin or tumor necrosis factor activated monocytes is enhanced by IgG from patients with lupus anticoagulant. 141 87

Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI). A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases. The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L. Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant. Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation. Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%). A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI. Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins. Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.
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PMID:Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. 207 76

Monocytes can play a role in the activation of coagulation via increased procoagulant activity (PCA). We investigated the level of monocyte PCA in 19 patients with systemic lupus erythematosus (SLE), given the high rate of thrombotic events in this condition. 9 of these subjects also presented the lupus anticoagulant (LA). The PCA generated by patient monocytes was significantly higher than control values and was identified as tissue factor-like. Serum from both groups of patients (i.e. SLE and SLE + LA) stimulated the generation of PCA by control monocytes. By contrast, purified IgG from both patient groups had the same effect as control IgG on PCA generation by control monocytes. The nature of the stimulating agent in the serum was not identified. In conclusion, increased monocyte PCA may account for the increased incidence of thrombosis in SLE patients, although other, superimposed, factors would appear to exist in SLE + LA patients, given the higher incidence of thrombosis in this subgroup.
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PMID:Increased monocyte procoagulant activity in patients with systemic lupus erythematosus. 209 14

Monocytes can play a role in the activation of coagulation via increased procoagulant activity (PCA). We investigated the level of monocyte PCA in 19 patients with systemic lupus erythematosus (SLE), given the high rate of thrombotic events in this condition. Nine of these subjects also presented the lupus anticoagulant (LA). The PCA generated by patient monocytes was significantly higher than control values and was identified as tissue factor-like. Moreover, the number of monocytes with membrane-associated D dimer, a parameter which we have shown to be correlated with the PCA expressed in vitro by endotoxin-activated monocytes, was also significantly increased. Serum from both groups of patients (i.e. SLE and SLE + LA) stimulated the generation of PCA by control monocytes. By contrast, purified IgG from both patient groups had the same effect as control IgG on PCA generation by control monocytes. The nature of the stimulating agent in the serum was not identified. In conclusion, increased monocyte PCA may account for the increased incidence of thrombosis in SLE patients, although other, superimposed, factors would appear to exist in SLE + LA patients, given the higher incidence of thrombosis in this subgroup.
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PMID:Increased monocyte procoagulant activity independent of the lupus anticoagulant in patients with systemic lupus erythematosus. 212 72

Antibodies that bind to endothelial cells have been identified in patients with diverse forms of vasculitis and thrombosis. Sera from patients with systemic lupus erythematosus contain both complement-fixing antibodies and immune complexes that bind to cultured endothelial cells. Sera from patients with heparin-associated thrombocytopenia and thrombosis contain antibodies that react with heparin bound to the endothelium and cross-react with heparan sulfate synthesized by endothelial cells. Children with Kawasaki syndrome may develop cytolytic IgM antibodies that recognize surface antigens induced on endothelial cells by interferon-gamma, interleukin 1, and tumor necrosis factor. The presence of alloantibodies to tissue-restricted polymorphic antigens expressed by endothelial cells is frequently associated with thrombotic microvascular injury and hyperacute allograft rejection. Binding of antibodies and immune complexes to endothelial cells in vitro initiates platelet adherence, production of tissue factor, and secretion of plasminogen activator inhibitor. Antibody-mediated endothelial cell injury may play a role in other vascular disorders of unknown cause.
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PMID:Disorders associated with antibodies to endothelial cells. 266 9

In order to evaluate the contribution of cellular immune mechanisms in the pathogenesis of immune complex-mediated glomerulonephritis, renal biopsies from 18 patients with lupus glomerulonephritis and 26 with cryoglobulinaemic glomerulonephritis were studied. Leucocyte profiles including T cell subsets and 'activated' macrophages within both glomeruli and interstitium were determined, using a panel of monoclonal antibodies as markers, and a sensitive 4-layer peroxidase technique to localize these within tissues. The infiltrating leucocytes were correlated with clinical, histological and immunological parameters of disease activity. Normal glomeruli contained few leucocytes though normal interstitium did (145 +/- 30 mm2), made up predominantly of T lymphocytes and macrophages. There was a significant increase in intraglomerular leucocytes in both systemic lupus erythematosus 4-fold, and essential mixed cryoglobulinaemia 7-fold, as compared to normal. These leucocytes consisted mainly of macrophages, and particularly in cryoglobulinaemia of 'activated' macrophages as demonstrated by their surface expression of the procoagulant tissue factor recognized by the A13 monoclonal antibody. In cryoglobulinaemic glomerulonephritis (GN) there was also a significant increase in T lymphocytes due to a predominance of suppressor-cytotoxic cells (OKT8+). There was a significant increase in interstitial leucocytes in both diseases, lymphocytes (mainly OKT8+ve), and macrophages (mainly 'activated' A13+ve). There were significant positive correlations between disease activity and interstitial leucocyte infiltration including, in lupus nephritis, degree of proteinuria and total leucocytes, hypocomplementaemia and T lymphocytes, increased numbers of monocytes and lymphocytes with a higher histological index of activity, and in cryoglobulinaemic GN of T lymphocytes and proliferative lesions, and T lymphocytes and C1q deposition. This study has demonstrated the importance of the interstitium in the pathogenesis of both diseases, delineated the presence of both T lymphocytes and activated monocytes which make cell-mediated immune mechanisms feasible, and linked the presence of immune mediators to disease activity.
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PMID:The relationship of infiltrating renal leucocytes to disease activity in lupus and cryoglobulinaemic glomerulonephritis. 317 97

Patients with systemic lupus erythematosus (SLE) have an increased incidence of arterial and venous thromboses. The mechanism by which thromboses develop in these patients is unknown. We had previously observed that the sera of patients with SLE contain antibodies and immune complexes that can bind to endothelial cells. Because endothelial cells can synthesize tissue factor, a potent activator of coagulation, we studied the effect of IgG complexes and sera from patients with SLE on the production of tissue factor by these cells. Human umbilical venous endothelial cells incubated with heat-aggregated IgG (HA-IgG) (0.5 to 4.0 mg) elaborate procoagulant activity in a dose-dependent manner. All procoagulant activity was found in the particulate cell fraction, and none was secreted into the medium. Maximum expression of procoagulant activity required 6 to 8 hr, and its production was totally inhibited by the addition of cyclohexamide or actinomycin D. The presence of gel-filtered platelets augmented production of procoagulant activity by endothelial cells stimulated by HA-IgG. Endothelial cell procoagulant activity was not inactivated by diisofluoropropylphosphate, required the presence of Factor VII for its expression, and was neutralized by a specific anti-tissue factor antibody. Endothelial cells incubated with sera from 14 of 16 patients with SLE produced increased amounts of tissue factor compared with 21 normal sera (p less than 0.025). Fractions of two SLE sera containing monomeric IgG, IgA, or IgM, as well as fractions containing IgG complexes, each stimulated endothelial cells to produce more tissue factor than similar fractions prepared from two normal sera. These studies demonstrate that endothelial cells will produce the procoagulant tissue factor after exposure to anti-endothelial cell antibodies or IgG-containing immune complexes. The production of tissue factor by endothelial cells at sites of immune vascular injury may play a role in the development of thromboses in patients with SLE.
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PMID:Antibody and immune complexes induce tissue factor production by human endothelial cells. 374 15

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

The original activated partial thromboplastin time-based assay for activated protein C (APC)-resistant factor Va (FVa) requires carefully prepared fresh plasma and cannot be used in patients receiving warfarin or in patients with antiphospholipid antibodies. A new test is described here that circumvents these limitations and distinguishes without overlap heterozygotes for APC-resistant FVa from persons with normal FV. A diluted test plasma is incubated with an FV-deficient substrate plasma and tissue factor and then clotted with Ca2+ or Ca2+ plus APC. Test results are independent of the FV level or the dilution of the test plasma used. Of 39 controls, 37 gave normal results. Two controls (5%) gave results indicative of APC resistant FVa and on DNA analysis were found to be heterozygous for FV R506Q. Twenty of 21 randomly selected patients receiving warfarin gave normal results. In the single patient with abnormal results, heterozygous FV R506Q was confirmed by DNA analysis. Two of 15 patients with protein S deficiency and 5 of 29 patients with a lupus anticoagulant had abnormal results. APC resistance caused by FV R506Q was confirmed in the five of these seven patients available for DNA analysis. APC-resistant FVa was also detected in 10 of 21 (46%) stored plasma from unrelated patients with venous thrombosis and negative earlier evaluation for a lupus anticoagulant or a deficiency of protein C, protein S, or antithrombin, which confirms a high incidence of this defect among patients with venous thrombosis.
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PMID:Use of a generally applicable tissue factor--dependent factor V assay to detect activated protein C-resistant factor Va in patients receiving warfarin and in patients with a lupus anticoagulant. 770 80

This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore, these are the defects which should first be searched for in an individual with unexplained thrombosis. If these more common defects are not found, the rarer defects, including HC-II, plasminogen, or TPA deficiency, dysfibrinogenemia, elevated PAI-1, or heterozygous homocystinemia should be looked for. The incidence of activated protein C co-factor deficiency (APC resistance) is not yet clear but may also represent a common defect. PAI-1 defects may, with time, be shown to be common. Finding these defects has important implications for therapy for the individual patient and for the institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks for thrombosis.
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PMID:Blood protein defects associated with thrombosis. Laboratory assessment. 778 Dec 75


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