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)

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

Antiphospholipid antibodies (aPL) are a family of autoantibodies with specificity for negatively charged phospholipids, or more accurately for their complex to phospholipid binding proteins. Their presence is associated with arterial/venous thrombosis and recurrent pregnancy loss. These clinical manifestations with the persistence of aPL are recognized as antiphospholipid syndrome(APS), one of the most common acquired thrombophilia. beta 2-glycoprotein I(beta 2GPI) bears the epitope(s) for anticardiolipin antibodies (aCL) on its molecule, and lupus anticoagulant activity depends on the presence of beta 2GPI or prothrombin. Thus phospholipid binding proteins may have some crucial roles in the pathophysiology of thrombotic events in APS. It has been hypothesized that aPL bind to cells and induce procoagulant activity via phospholipid binding proteins.
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PMID:[Antiphospholipid syndrome]. 946 93

Antiphospholipid antibodies (aPL) are a family of autoantibodies with specificity for negatively charged phospholipids, or more accurately for their complex to phospholipid binding proteins. Their presence is associated with arterial/venous thrombosis and recurrent pregnancy loss. These clinical manifestations with the persistence of aPL are recognized as antiphospholipid syndrome (APS), one of the most common acquired thrombophilia. beta 2-glycoprotein I (beta 2GPI) bears the epitope(s) for anticardiolipin antibodies (aCL) on its molecule, and lupus anticoagulant activity depends on the presence of beta 2GPI or prothrombin. Thus phospholipid binding proteins may have some crucial roles in the pathophysiology of thrombotic events in APS.
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PMID:[Clinical significance of antiphospholipid antibodies]. 959 18

Antiphospholipid antibodies have been demonstrated in chronic hepatitis C, but their clinical and pathogenetic significance remains elusive. We prospectively studied 115 patients (85 men, mean age 36.9 years) with chronic hepatitis C without cirrhosis and treated by alpha-interferon (alpha-IFN). Antiphospholipid determinations comprised anticardiolipin (ACA), anti-beta2-glycoprotein I and anti-prothrombin antibodies of the IgG and IgM classes. At entry, 24 patients (21%) were found to possess low to moderate ACA levels (18 IgG, two IgM and four both isotypes) compared with only 4/115 age- and sex-matched control subjects (3.5% P=0.001). ACA positivity rate increased to 31% (P=0.01) after a 6-month course of alpha-IFN treatment. In contrast, the prevalence of anti-beta2-glycoprotein I and anti-prothrombin antibodies was not significantly different from controls at either time point. The presence of ACA correlated with that of antinuclear antibodies (P=0.0002), but was not associated with parameters such as histological activity, viral burden and response to alpha-IFN, nor with a history of thrombosis or pregnancy loss. However, a non-significant trend of higher incidence of mild thrombocytopenia among ACA-positive patients was observed. We conclude that low-titre ACA positivity is a common finding in patients with chronic hepatitis C, especially following alpha-IFN treatment, but does not select a category with different clinical features. These data are in keeping with the absence of associated anti-beta2GPI and anti-prothrombin antibodies, and do not support a role for HCV infection in the pathogenesis of the antiphospholipid syndrome.
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PMID:Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and anti-prothrombin antibodies in chronic hepatitis C. 963 88

Lupus anticoagulant (LA) antibodies have been shown to be directed to protein-phospholipid complexes. In this study, we report on LA antibodies from patients with the 'antiphospholipid' syndrome (APS), that are directed to prothrombin and beta2-glycoprotein I, but not to the complexes of these plasma proteins to anionic phospholipids. The anti-prothrombin antibodies studied had different reactivities in two clotting assays: the dilute Russell's viper venom time (dRVVT) and the dilute kaolin clotting time (dKCT). Anti-prothrombin and anti-beta2-glycoprotein I (anti-beta2GPI) antibodies, affinity-purified from one patient with APS were not cross-reactive and had different effects in the dRVVT and dKCT clotting tests. Polyclonal anti-prothrombin antibodies, affinity-purified on a prothrombin column, from two patients with prothrombin reactivity in their plasma, have affinity constants to prothrombin of 104 and 192 nM. The patient with affinity-purified antibodies to prothrombin and beta2GPI, had affinity constants to prothrombin and beta2GPI, respectively, of 192 nM and 3030 nM, respectively. LA antibodies are a heterogeneous population of antibodies that have different immunological specificities and clotting test reactivities in different patients.
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PMID:Anti-beta2-glycoprotein I and anti-prothrombin antibodies in patients with the 'antiphospholipid' syndrome: immunological specificity and clotting profiles. 969 36

The antiphospholipid syndrome is a thrombophilic condition marked by antibodies that recognize anionic phospholipid-protein cofactor complexes. We recently reported that exposure to IgG fractions from antiphospholipid patients reduces the level of annexin-V, a phospholipid-binding anticoagulant protein, on cultured trophoblasts and endothelial cells and accelerates coagulation of plasma exposed to these cells. Therefore, we asked whether antiphospholipid antibodies might directly reduce annexin-V binding to noncellular phospholipid substrates. Using ellipsometry, we found that antiphospholipid IgGs reduce the quantity of annexin-V bound to phospholipid bilayers; this reduction is dependent on the presence of beta2-glycoprotein I. Also, exposure to plasmas containing antiphospholipid antibodies reduces annexin-V binding to phosphatidyl serine-coated microtiter plates, frozen thawed washed platelets, activated partial thromboplastin time (aPTT) reagent and prothrombin time reagent and reduces the anticoagulant effect of the protein. These studies show that antiphospholipid antibodies interfere with the binding of annexin-V to anionic phospholipid and with its anticoagulant activity. This acceleration of coagulation, due to reduced binding of annexin V, stands in marked contrast to the "lupus anticoagulant effect" previously described in these patients. These results are the first direct demonstration of the displacement of annexin-V and the consequent acceleration of coagulation on noncellular phospholipid surfaces by antiphospholipid antibodies.
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PMID:Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a "lupus procoagulant" phenomenon. 971 93

Antiphospholipid antibodies associated with the antiphospholipid syndrome (APS) have been shown to bind plasma proteins, particularly beta 2-glycoprotein I (beta2-GPI). In this study the incidence of antibodies to solid-phase prothrombin was examined in patients with antiphospholipid syndrome and a variety of other inflammatory disorders. Significantly elevated levels of IgG anti-prothrombin (anti-PT) antibodies were detected in 63% of patients with APS (n = 27, median 22 arbitrary units: AU), 33% with SLE (n = 92, median 14 AU). 45% with rheumatoid factor (n = 22, median 16 AU), 21% with carotid artery stenosis (n = 21, median 15 AU), 32% with stroke (n = 38, median 13 AU). 67% of patients with a false positive serology for syphilis (n = 21, median 24 AU), 37% with HIV (n = 30, median 14 AU), 29% with syphilis (n = 14, median 19 AU) and 3% with infectious mononucleosis (n= 30, median 9 AU). In addition, a group of lupus anticoagulant (LA) positive patients (n = 48) was examined for antibodies to prothrombin, beta2-GPI and cardiolipin. 10 (21%) patients had raised levels of IgG anti-PT antibodies, 30 (62%) had significantly elevated levels of anti-beta2-GPI antibodies and 15 (31%) had elevated levels of anticardiolipin antibodies (ACA). Of the LA-positive patients, 15 (43%) were identified with definite APS, eight (23%) with probable APS, two (6%) with possible APS and 10 (28%) patients had no clinical evidence of APS. In conclusion, antibodies to prothrombin were found in a variety of inflammatory disorders and were therefore not specific for the APS. However, identification of the plasma proteins recognized by antibodies from patients with APS may provide insight into the pathogenic mechanisms involved in the heterogenous clinical manifestations of the APS.
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PMID:Antibodies to prothrombin in antiphospholipid syndrome and inflammatory disorders. 973 36

Lupus anticoagulant antibodies form a heterogeneous group of antiphospholipid antibodies with rather poorly defined antigens. The role that phospholipid-binding proteins play in lupus anticoagulant antibody activity is a subject of current investigation. Several candidate proteins have been proposed, including beta2-glycoprotein I (beta2GPI), prothrombin, and annexin V. As beta2GPI-dependent lupus anticoagulants will be reviewed elsewhere in this issue, this paper will focus on the involvement of prothrombin and annexin V in lupus anticoagulant activity. Evidence for a role for these proteins in the reactivity and induction of lupus anticoagulant antibodies will be discussed, as well as an apparent requirement for both phospholipid and phospholipid-binding protein. The data presented here suggest that some lupus anticoagulant antibodies recognize and may be induced by complexes of phospholipid and phospholipid-binding proteins, in particular, phospholipid and prothrombin or annexin V.
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PMID:Lupus anticoagulant antibodies: recognition of phospholipid-binding protein complexes. 981 68

Prothrombin is a common antigenic target of antiphospholipid antibodies, since anti-prothrombin antibodies are detected in about 50-90% of the patients. To allow proper immune recognition, prothrombin must be adsorbed on suitable anionic surfaces. The epitope(s) have not yet been identified: the majority of anti-prothrombin antibodies appear to be of poly- or oligoclonal nature. Anti-prothrombin antibodies, either alone or in combination with anti-beta2-glycoprotein I antibodies, are responsible for the lupus anticoagulant activity of about 75% of the cases of phospholipid-dependent inhibitors of coagulation. The two antibodies may be discriminated by means of specific coagulation profiles generated by the comparison of the ratio of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): the KCT profile, which mainly reflects the presence of anti-prothrombin antibodies and the dRVVT profile, which is mostly associated with anti-beta2-glycoprotein I antibodies. This distinction, although somewhat artificial, may be clinically useful, since the KCT profile identifies patients at low risk to develop thrombosis. Similarly, most of the studies that measured anti-prothrombin antibodies by ELISA failed to find a significant association with thrombosis. In conclusion, the clinical relevance of these antibodies has not yet been established.
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PMID:Prothrombin as cofactor for antiphospholipids. 981 70

It is widely hypothesized that autoantibodies directly contribute to the prothrombotic state in the antiphospholipid syndrome (APS). The discovery that antiphospholipid autoantibodies are specific for phospholipid-binding plasma proteins (beta2-glycoprotein I, prothrombin, etc.) has allowed a much more precise investigation of the interactions of autoantibodies and antigens, and the effects of these interaction on hemostasis. Recent studies suggest that two types of interactions may be important in the pathophysiology of APS: (1) antibody cross-linking of membrane bound antigens may alter the kinetics of phospholipid-dependent reactions; and (2) antibody cross-linking of antigens bound to cell surface receptors may trigger signal transduction and cellular activation. In light of these findings, previous reports implicating various mechanisms of autoantibody-mediated thrombosis are being re-evaluated.
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PMID:Mechanisms of autoantibody-mediated thrombosis. 981 87


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