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)

The primary antiphospholipid antibody syndrome is characterized clinically by the presence of venous and arterial thrombosis, recurrent fetal loss, and thrombocytopenia. The presence of antiphospholipid antibodies is a central serologic finding in primary antiphospholipid antibody syndrome, and plays a critical role in diagnosis. Contrary to initial reports, it is now widely accepted that these autoantibodies are directed predominantly against two antigens: phospholipid-binding plasma protein beta2-glycoprotein I and prothrombin. The mechanism by which antiphospholipid antibodies cause disease is under vigorous investigation. It is hypothesized that antiphospholipid antibodies induce a procoagulant state by binding to antigens on endothelial cells and trophoblast cell surfaces. Indeed, beta2-glycoprotein I appears to function as a cofactor that facilitates this interaction. The resulting endothelial cell activation is associated with cell-surface expression of adhesion molecules that lead to monocyte adhesion - the first steps in thrombosis. Although the precise mechanism that mediates endothelial cell-platelet interaction have not been fully elucidated, platelet binding to the endothelium appears to be the next phase in thrombosis. Thus, the antiphospholipid antibody may be a triggering or activating factor in placental spiral artery thrombosis and subsequent placental infarction. More recently, a role for annexin V has emerged. Studies suggest that thrombosis in the antiphospholipid syndrome may be due to disruption of the annexin shield by antiphospholipid (and cofactor) antibodies, which results in the increased exposure of trophoblasts and endothelial cells to thrombogenic phospholipids.
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PMID:Immunopathogenesis of the antiphospholipid antibody syndrome: an update. 1134 97

We investigated the mechanism by which anti-prothrombin antibodies cause lupus anticoagulant (LAC) activity. Addition of affinity-purified anti-prothrombin antibodies from LAC-positive plasma samples (alpha-FII-LAC+) to normal plasma induced LAC activity. Upon increasing the phospholipid concentration, LAC activity was neutralized. Addition of purified alpha-FII-LAC+ to normal plasma strongly inhibited factor Xa formation. No inhibition was measured when alpha-FII-LAC+ were added to prothrombin-deficient plasma or when purified anti-prothrombin antibodies from LAC-negative plasma samples (alpha-FII-LAC-) were added. When a combination of prothrombin and alpha-FII-LAC+ was added to the purified clotting complex, a strong inhibition of factor Xa and IIa formation was seen. The alpha-FII-LAC+ alone or a combination of prothrombin and alpha-FII-LAC- did not show inhibition. Ellipsometry studies showed that, in the presence of alpha-FII-LAC+, the affinity of prothrombin for a phospholipid surface increased dramatically, whereas a much lower increase was observed with alpha-FII-LAC-. Our results show that complexes of prothrombin and anti-prothrombin antibodies with LAC activity inhibit both prothrombinase and tenase. The antibodies increase the affinity of prothrombin for the phospholipid surface, thereby competing with clotting factors for the available catalytic phospholipid surface, a mechanism similar to that of anti-beta2-glycoprotein I antibodies.
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PMID:Complexes of anti-prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces. 1138 Apr 47

Anti-prothrombin antibodies (anti-prothrombin) and anti-beta2-glycoprotein I antibodies (anti-beta2-GP I) are the most common and characterized anti-phospholipid antibodies (aPL) detected using specific enzyme-linked immunosorbent assay (ELISA) systems. Recently, lupus anti-coagulant (LA) activity detected by a phospholipid-dependent coagulation assay was reported to be associated with anti-prothrombin and/or anti-beta2-GP I. Here we show that the co-existence of IgG anti-prothrombin and LA activity might be an essential risk factor for venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE). We examined not only the levels of antibodies to prothrombin and anti-beta2-GP I (both IgG and IgM isotypes) using an ELISA system, but also LA activity detected using both diluted Russell's viper venom time (dRVVT) and STACLOT LA test in 124 patients with SLE. The SLE patients were divided into four groups according to the results of ELISA and LA assay results for each aPL: group A, ELISA+ and LA+ group B, ELISA+ and LA-; group C, ELISA- and LA+ group D, ELISA- and LA-. Regarding IgG anti-prothrombin, the prevalence of VTE was significantly higher in group A (16/35 cases, 45.7%, P < 0.001, Fisher's exact probability test) than in the other groups (B, 2/30, 6.7%; C, 1/22, 4.5%; D, 1/37, 2.7%). With respect to IgM anti-prothrombin and IgG or IgM anti-beta2-GP I, the prevalence of VTE was higher in both groups A and C than in group D, but no statistical difference in prevalence was found between groups A and C. Multivariate logistic regression analysis of risk factors for VTE confirmed that the co-existence of IgG anti-prothrombin and LA activity was the only significant risk factor for VTE (odds ratio, 19.13; 95% confidence intervals, 4.74-77.18).
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PMID:Anti-prothrombin antibodies combined with lupus anti-coagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus. 1155 93

The antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis, recurrent pregnancy loss, and thrombocytopenia combined with laboratory tests that indicate the presence of antibodies against phospholipid-binding proteins. The antibodies are directed against a complex of phospholipid with a protein such as beta 2-glycoprotein I (beta 2-GPI) or prothrombin and are detected by means of phospholipid-dependent coagulation assays (known as assays for lupus anticoagulants) and by ELISAs that contain beta 2-GPI and a phospholipid (e.g., cardiolipin). The antiphospholipid syndrome can be associated with other connective tissue disorders such as systemic lupus erythematosus or may be the only manifestation of an autoimmune disorder. Management of patients with this disorder usually includes anticoagulation, which has been found to reduce the rate of recurrence of venous and arterial thrombosis as well as the rate of fetal loss.
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PMID:Diagnosis and management of patients with the antiphospholipid syndrome. 1171 94

Patients with the anti-phospholipid syndrome (APS) have antiphospholipid antibodies (aPA) which are often targeted towards phospholipid binding proteins such as beta2-glycoprotein I and prothrombin. Antibodies to factor XII (FXIIabs) have also been identified in some patients with APS. Factor XII (FXII) is a member of the kringle family of proteins which include plasminogen and prothrombin. Antibodies to prothrombin have been associated with myocardial infarction and have been shown to cross react with plasminogen. Sixteen patients with APS and FXIIabs were investigated for the presence of antibodies to prothrombin, by enzyme linked immunosorbent assay in a calcium (Ca++) independent assay. All sixteen showed different antibody binding patterns than those observed for antibodies to FXII. Eight patients were further investigated using surface plasmon resonance (SPR) for antibody binding to covalently bound FXII and to covalently bound prothrombin in both Ca++ dependent and independent systems. Of three patients demonstrating antibody binding to FXII by SPR, none demonstrated antibody binding to prothrombin in a Ca++ independent system with one demonstrating antibody binding to prothrombin that was Ca++ dependent. Of five patients who did not bind FXII by SPR, one demonstrated antibody binding to prothrombin in a Ca++ independent system while two demonstrated antibody binding to prothrombin in a Ca++ dependent system. Antibodies to FXII in patients with APS appear to be distinct from antibodies to prothrombin.
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PMID:Antibodies to factor XII are distinct from antibodies to prothrombin in patients with the anti-phospholipid syndrome. 1191 74

The presence of lupus anticoagulants (LAC) in plasma is a major risk factor for thrombosis. An attractive hypothesis to explain a LAC-mediated thrombotic tendency is that LAC interfere with activation of protein C, a natural antithrombotic in plasma. We investigated the relationship between LAC and protein C activation in vivo. We selected 20 patients with systemic lupus erythematosus (SLE) with LAC (and not using oral anticoagulants), 36 patients with SLE without LAC and 25 healthy volunteers. In these, we measured circulating levels of activated protein C (APC), prothrombin (FII), free protein S, C4BP, protein C, and antibodies to protein C, protein S, FII and beta2-glycoprotein I (beta2GPI). In SLE patients (n = 56), mean levels of APC, FII and free protein S were significantly (P < 0.001) lower than those in healthy volunteers (respectively 13%, 17% and 14%). Mean protein C levels and C4BP levels were similar for SLE patients and healthy volunteers. In contrast to the above hypothesis, the decreased levels of APC could not be attributed to the presence of LAC. Levels of APC were correlated with both FII levels and protein C levels. Decreased levels of APC, FII, protein C and free protein S were related to the presence of anti-FII antibodies. None of the patients had antibodies against protein C or protein S. In conclusion, although the mean levels of APC, FII and free protein S were significantly decreased in SLE patients, no correlation with LAC was found. However, anti-FII antibodies were related to decreased levels of APC, FII, protein C, free protein S and C4BP. As FII levels, and not protein C levels, were decreased in SLE patients and correlated with APC levels, we conclude that the decreased FII levels are responsible for the low levels of APC.
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PMID:Low levels of activated protein C in patients with systemic lupus erythematosus do not relate to lupus anticoagulants but to low levels of factor II. 1202 41

The antiphospholipid syndrome (APS) is a thrombotic disorder leading to spontaneous abortions, venous thromboses, myocardial infarctions and strokes. Although the syndrome is associated with characteristic autoantibodies, these tests have poor predictive value for thrombosis. The aim of the study was to determine whether the combined presence of two types of antiphospholipid antibodies can be associated with a high-risk subset of thrombosis-prone patients. One hundred and thirty-four sera from a lupus clinic were tested for antibodies to beta2-glycoprotein I (beta2GPI), protein S and prothrombin. In a group of 29 patients for whom plasma was available, free (functional) protein S levels were also measured. Autoantibodies to beta2GPI and protein S are associated with each other. Dual reactivity to beta2GPI and protein S correlates with increased history of thrombotic events (69% of doubly reactive patients) when compared to either type of autoantibody alone (37% of patients with only anti-beta2GPI and 38% with only anti-protein S, P=0.04 and P=0.01, respectively) or neither reactivity (37%). Among 29 patients tested for free (functional, anticoagulant) protein S levels, the lowest levels were found in patients with antibodies to beta2GPI and/or protein S, and all four patients with a history of thrombosis had below-normal free protein S levels. These associations were not found with antiprothrombin antibodies. In conclusion dual autoantibodies to beta2GPI and protein S are associated with increased history of thrombosis in the antiphospholipid syndrome.
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PMID:Dual antibody reactivity to beta2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome. 1204 84

Venous thromboembolism (VTE) is one of the common manifestations in the anti-phospholipid (aPL) syndrome. We examined the levels of IgG antibodies (Abs) to beta2-glycoprotein I (beta2-GP I) and prothrombin, lupus anticoagulant (LA) activity, activated protein C resistance (APC-R), and factor V Leiden in 96 patients with systemic lupus erythematosus (SLE); 19 with VTE and 77 without VTE. Acquired APC-R, which was not found in any patient with the factor V Leiden mutation, was present in 33 (34.4%) out of the 96 patients with SLE. The presence of acquired APC-R was a strong risk factor for VTE. The SLE patients were divided into four groups according to the results of enzyme-linked immunosorbent assay (ELISA) and LA activity for each aPL Abs: ELISA+, LA+; ELISA+, LA-; ELISA-, LA+; and ELISA-, LA-. A significant association was observed between APC-R and the co-existence of anti-beta2-GP I Abs and LA activity or of anti-prothrombin Abs and LA activity. There was no association between APC-R and the presence of anti-beta2-GP I Abs, anti-prothrombin Abs, or LA activity alone. However, when multivariate logistical regression analysis was performed, it was clear that only the co-existence of anti-prothrombin and LA activity was a significant risk factor for APC-R. These findings indicate that the co-existence of anti-prothrombin Abs and LA activity may be an important factor in the pathogenesis of acquired APC-R in patients with SLE.
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PMID:Acquired activated protein C resistance is associated with the co-existence of anti-prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus. 1271 80

Anti-phospholipid (aPL) antibodies (Abs) are well known to be associated with thromboembolic events in patients with systemic lupus erythematosus (SLE). However, the clinical relevance of a PL Abs in patients without SLE (non-SLE) who have venous thromboembolism remains unclear. We evaluated 143 non-SLE patients with a first episode of clinically suspected deep vein thrombosis (DVT) by using objective tests for diagnosing DVT and laboratory tests including the activated protein C resistance (APC-R) test, the factor V Leiden test, and various aPL Abs. The prevalence of acquired APC-R, in which case there was no factor V Leiden mutation, was significantly higher in patients with DVT (15/58 cases, 25.9%, p < 0.0001) than in those without DVT (3/80 cases, 3.7%), and confirmed that acquired APC-R was a strong risk factor for DVT (odds ratio [OR], 8.95; 95% confidence intervals [CI], 2.45-32.7; p < 0.001). Multivariate logistic analysis revealed that the presence of LA, aCL, anti-beta2-glycoprotein I, anti-prothrombin and anti-protein C Abs was not reliable as a risk factor for DVT in non-SLE patients, and that the presence of anti-protein S Abs was the most significant risk factor for DVT (OR, 5.88; 95% CI, 1.96-17.7; p < 0.002). Furthermore, the presence of anti-protein S Abs was strongly associated with acquired APC-R (OR, 57.8; 95% CI, 8.53-391; p < 0.0001). These results suggest that acquired APC-R may reflect functional interference by anti-protein S Abs of the protein C pathway, which action may represent an important mechanism for the development DVT in non-SLE patients.
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PMID:Acquired activated protein C resistance associated with anti-protein S antibody as a strong risk factor for DVT in non-SLE patients. 1242 83

We performed a case-control study to assess whether anti-beta2-glycoprotein I and anti-prothrombin antibodies are independent risk factors of thrombosis. Cases were 79 patients with arterial and/or venous thrombosis without lupus anticoagulants, anticardiolipin antibodies and systemic lupus erythematosus; controls were 85 normal subjects. The prevalences and titers of IgG and IgM anti-beta2-glycoprotein I and anti-prothrombin antibodies were similar in both groups. Cases were analyzed with respect to the arterial or venous type of thrombosis and to the presence of congenital or acquired risk factors for thrombosis: no statistically significant relationships with the presence of anti-beta2-glycoprotein I and anti-prothrombin antibodies were found. Our data indicate that anti-beta2-glycoprotein I and anti-prothrombin antibodies are not risk factors for thrombosis independent of lupus anticoagulants and anticardiolipin antibodies. Their measurement, therefore, is not warranted in the laboratory screening of patients with arterial and/or venous thrombosis.
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PMID:Anti-beta2-glycoprotein I and anti-prothrombin antibodies in antiphospholipid-negative patients with thrombosis: a case control study. 1242 85


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