Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We developed an ELISA to quantitate complexes of activated protein C (APC) with a major plasma APC inhibitor, alpha 1-antitrypsin (alpha 1AT) in human plasma based on the sandwich principle using two different antibodies directed towards protein C and alpha 1AT, respectively. This ELISA test was specific for APC:alpha 1AT complexes and sensitive to greater than or equal to 150 pg complex. Fifty-one of 56 healthy donors had APC:alpha 1AT complex levels above the detection limit (3 ng/ml) ranging from 4 to 14 ng/ml (mean value +/- SD: 7.6 +/- 2.5 ng/ml). Patients (n = 10) with disseminated intravascular coagulation (DIC) had detectable levels of APC:alpha 1AT complex ranging from 21 to 125 ng/ml (median: 69 ng/ml). Complexes of APC with plasma protein C inhibitor (PCI) were also measured using an ELISA sandwich assay. None of the 30 healthy donors had detectable levels (greater than or equal to 5 ng/ml) of APC:PCI complex, and plasma samples from 9 of 10 DIC patients had detectable concentrations of APC:PCI complex ranging from 10 to 63 ng/ml (median: 22 ng/ml). APC:alpha 1AT complex was detected in 25 of 26 patients with deep venous thrombosis (DVT), with levels ranging from 5 to 136 ng/ml (median: 23 ng/ml), whereas APC:PCI was detected in only 6 DVT patients, with levels between 11 and 105 ng/ml. PCI antigen levels in 70 normals ranged from 56 to 175% (mean +/- SD: 99.1% +/- 24.2%). PCI antigen levels were decreased in DIC patients, in patients with cerebral arterial thrombosis, and in DVT patients undergoing heparin therapy, but not in patients with myocardial infarction. PCI antigen levels were decreased much further in DVT patients receiving heparin compared to those not receiving heparin, showing that heparin therapy is associated with a decrease in PCI levels. The detection in normal subjects and in thrombotic patients of circulating APC:inhibitor complexes supports the view that the protein C pathway is activated during DIC and DVT. Moreover, it emphasizes that both PCI and alpha 1AT are physiologic inhibitors of APC. Thus, measurement of APC complexes may provide sensitive parameters for specific detection of activation of the clotting and protein C pathways.
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PMID:Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. 217 67

Clinical and serological features in SLE patients with arterial or venous thrombosis were studied. The subjects consisted of 140 patients with SLE who met the revised criteria for the classification of SLE by the American Rheumatism Association. Forty patients (29%) had arterial or venous thrombosis. Arterial thrombosis such as stroke was found in 30 patients, and venous thrombosis such as deep vein thrombosis was seen in 24 patients. Average age at the disease onset was 34.5 +/- 12.5 years old. Renal disorder was found as a clinical feature, and IgG anticardiolipin antibodies (aCL), IgG phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies and IgG anti-Annexin V antibodies were identified as serological features in SLE patients with thrombosis. These patients were diagnosed as having antiphospholipid syndrome. It was necessary to perform primary prevention therapy as well as secondary prevention therapy. Multiple thrombotic events in the past history and sustained positive reactions of IgG aCL were suggested as predictors of recurrent thrombosis. These data indicated the clinical and serological characteristics in SLE patients with arterial or venous thrombosis.
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PMID:[Thrombosis in patients with SLE and antiphospholipid syndrome]. 778 37

We studied sera from patients with various disorders including collagen diseases, Buerger's disease, deep vein thrombosis, repeated abortions and idiopathic thrombocytopenic purpura in order to measure anticardiolipin antibody (aCL) titers. In our assay system, we can detect aCL against bovine cardiolipin and the complex of cardiolipin and beta 2-glycoprotein I (beta 2-GPI). This was done with simultaneous assays using blank wells and bovine cardiolipin coated wells in the EIA method in which both wells were also coated with bovine serum albumin possibly containing beta 2-GPI, then aCL titers was given by subtraction of O.D. values of blank wells from those of cardiolipin coated wells. When the aCL was quantified by anti human immunoglobulin antibodies, collagen diseases showed positive aCL in 15 (11.5%) out of 130 sera with positive anti ENA antibodies, 3 (11.1%) out of 27 sera with positive anti DNA antibodies and 3 (5.2%) out of 58 sera with other positive ANA sera. The other hand, we found positive aCL in 2 (4.9%) out of 41 sera from patients with Buerger's disease, 4 (36.4%) out of 11 sera from patients with deep vein thrombosis, 1 (7.7%) out of 13 sera from patients with repeated abortions and 6 (14.6%) out of 41 sera from patients with idiopathic thrombocytopenic purpura. Twenty one (61.8%) out of these aCL positive sera had also positive IgG-aCL for the assay using anti human IgG antibody. Compared to previous reports, we thought, low incidence of aCL in our study was due to exclusion of anti beta 2-GPI antibody in our assay system.
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PMID:[Detection of anticardiolipin antibody using the EIA kit prepared to eliminate interference of serum cofactor]. 837 6

There is accumulating evidence that anti-phospholipid (aPL) antibodies in the sera of patients with autoimmune diseases bind to a complex of anionic phospholipids and plasma phospholipid-binding proteins, namely beta 2-glycoprotein I (beta 2-GPI) and prothrombin. It has been suggested that a conformational change in beta 2-GPI, induced by binding either to anionic phospholipids or to the oxygen molecules on the irradiated microtiter plate, reveals cryptic antigenic epitope(s) in the native protein. We used an enzyme-linked immunoassay for measuring antibodies against two phospholipid-binding proteins, i.e., beta 2-GPI and prothrombin, absorbed to an irradiated plate in an unselected series of 139 patients with systemic lupus erythematosus (SLE). Elevated levels of antibodies against beta 2-GPI were found in 49% of patients and antibodies against prothrombin in 34% of patients. Both antibodies were significantly associated with deep venous thrombosis in patients with SLE (P = 0.009 for both antibodies). Accordingly, testing of these antibodies seems to be clinically useful in evaluating the risk of thrombosis.
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PMID:Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus. 867 35

There has been a recent, dramatic surge in interest in antiphospholipid antibodies and associated clinical disorders, especially focal ischemic cerebrovascular disease. Antiphospholipid antibodies are a heterogeneous group of antibodies with varying specificities. Coagulation assays will detect lupus anticoagulants while enzyme-linked immunosorbent assays detect anticardiolipin antibodies. There are numerous potential links between antiphospholipid antibodies and coagulation disorders, including interaction of antiphospholipid antibodies and a cofactor, beta 2-glycoprotein I, which itself is involved in coagulation mechanisms. While the specific mechanism of antiphospholipid antibody-related coagulopathy is unknown, it is clear that antiphospholipid antibodies are associated with an immune-mediated prothrombotic state. Patients with the highest titers of IgG antiphospholipid antibodies have a relatively high risk of recurrent thrombotic events, especially stroke, deep venous thrombosis, and spontaneous abortion. Because of limited controlled, prospective data, current therapy remains empiric and directed at coagulation mechanisms, immune mechanisms, or both.
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PMID:Cerebrovascular disease with antiphospholipid antibodies: immune mechanisms, significance, and therapeutic options. 896 22

During late seventies it became apparent that the appearance of antiphospholipid antibodies is associated with thromboembolic manifestations, such as cerebral or myocardial infarction, pulmonary thromboembolism, deep vein thrombosis, intrauterine fetal losses and thrombocytopenia. The term antiphospholipid syndrome has been used to define this set of pathologic features. Recognition of this syndrome has spread worldwide as its clinical implications have become appreciated. Recent studies showed that cofactor, beta 2-glycoprotein I (beta 2-GPI) is required for binding of anticardiolipin antibodies (aCL) raised in the patients with SLE and related other autoimmune disorders. However, this finding has generated considerable controversy. Four different hypotheses have been proposed to explain the specificity of aCL: (1) CL is directly recognized by aCL; (2) the beta 2-GPI-CL complex is the structure recognized by aCL; (3) the beta 2-GPI is the actual target antigen for aCL but is cryptic in the absence of CL; and (4) the actual epitope for aCL appears on the native structure of beta 2-GPI. We showed that aCL bound to beta 2-GPI interacting with poly-oxygenated plates and in the absence of CL, an interaction which depends on introduction of oxygen atoms on the polystyrene surface. We also showed that the beta 2-GPI bound to CL via a particular region on the fifth domain, namely C281KNKEKKC288, and the tertiary structure of the region is involved in binding to phospholipid. Several mechanisms to explain the vascular injury and thrombosis associated with aCL have been proposed, primarily based on their phospholipid reactivity to activated platelets. Whether aCL-through binding to complex of beta 2-GPI and negatively charged phospholipid in the phospholipid-dependent coagulation reactions of hemostasis contribute to the increased risk of thrombosis in patients with aCL is an important question in need of an answer. We have demonstrated the possibility that not only activated platelets but also oxidized lipoproteins, e.g., low-density lipoprotein (LDL), may be thrombogenic targets of aCL which recognize the altered beta 2-GPI structure.
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PMID:[Autoantibodies and thrombosis]. 936 65

Antibodies against phospholipid-binding plasma proteins, such as beta2-glycoprotein I (beta2-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes.
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PMID:High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men--a nested case-control study. 936 81

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.
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PMID:Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease. 982 43

To establish the prevalence of antibodies against beta2-glycoprotein I (beta2GPI) in unselected patients with venous thromboembolism, as well as the association with antiphospholipid antibodies (aPL) and a history of previous thromboembolism, we investigated the presence of these antibodies in 227 consecutive patients with acute deep vein thrombosis or pulmonary embolism, of whom 63 were carriers of aPL with or without lupus anticoagulant (LA), and seven were carriers of LA alone. The presence of antibodies against beta2GPI was demonstrated in 19 patients [8.4%; 95% confidence interval (CI), 4.5-11.3%]. All of them belonged to the group of 63 patients with aPL (30.2%). A history of a previous thromboembolism was identified in 11 of the 19 patients with anti-beta2GPI antibodies (57.9%) and in 45 of the 208 patients without these antibodies [21.6%; odds ratio (OR)=4.98; 95% CI, 1.89-13.1; p<0.0005]. In the subgroup of patients with aPL and/or LA, the rate of recurrent thromboembolism among patients with anti-beta2GPI antibodies (11 of 19, 57.9%) was significantly higher than that observed in patients without these antibodies (15 of 51, 29.4%; OR=3.3; 95% CI, 1.1-9.83; p=0.28). We conclude that in patients with acute venous thromboembolism the prevalence of antibodies against beta2GPI is unexpectedly high. The presence of these antibodies seems to identify a subgroup of patients with antiphospholipid antibodies who have a peculiarly high risk of thrombotic recurrences. Further prospective studies are indicated to better define the role of anti-beta2GPI antibodies in the development of recurrent thromboembolism.
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PMID:Anti-beta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism. 1059 29

Antiphospholipid antibodies (APAs) are considered risk factors in patients with thromboembolic diseases. Although the incidence of such acquired coagulation disturbances in adults are well described, only few data exist for children. Therefore, in a first step to collect new data we analyzed the presence of different APAs in 202 consecutive children and compared them with two groups of adults. The children screened for APA were exclusively those who did not have any thromboembolic complications or a tendency for thrombophilia due to other underlying diseases such as systemic lupus or malignancy in their past or present medical history. Consecutive blood samples were evaluated from routine laboratory specimens. The two groups of adults comprised 200 patients after deep vein thrombosis and 200 patients without thromboembolic events that served as controls. Four lupus anticoagulant (LA) screening tests were determined: the dilute Russell's viper venom test; a lupus anticoagulant-sensitive activated partial thromboplastin time reagent; a second lupus-sensitive activated partial thromboplastin time; and the Kaolin clotting time. Furthermore, three different antiphospholipid antibodies ELISA assays against cardiolipin (ACA), beta2-glycoprotein I, and phosphatidyl-serine, were determined. The children had a much higher prevalence for LA than did the adults. On the other hand, their values for ACA were significantly lower than in adults with a history of thromboembolism. Findings in children were similar to the normal adult group. This has to be taken into account when evaluating children with thromboembolic diseases.
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PMID:Antiphospholipid antibodies in children without and in adults with and without thrombophilia. 1129 Dec 89


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