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)

Individuals with severe factor XII (FXII) deficiency may be prone to thromboembolic disease and this thrombophilic state may be due to insufficient contact activation dependent fibrinolysis. According to our previous study (Thromb Haemostas 1991; 65: 117-121), however, heterozygous FXII deficiency is not a strong prethrombotic risk factor, only one out of 45 obligatory or possible heterozygotes having sustained a thrombotic event. In the present study, FXII clotting activity (FXII:C) and antigen concentration (FXII:AG) were measured in 200 patients having suffered from idiopathic thromboembolism and compared with the values in 200 healthy controls. Mean FXII levels were not significantly different in thrombophilic patients and controls, and subnormal FXII values were not more frequently encountered in patients than in controls. Specific FXII activity, i.e. the ratio of FXII:C to FXII:AG, showed considerable variation in each of the two groups, but patients and controls had a similar distribution of specific FXII activity. Variations in specific FXII activity were not explained by differences in beta 2-glycoprotein I levels. In conclusion, heterozygous FXII deficiency is not a strong prethrombotic risk factor and subnormal FXII values are not more common in thrombophilic patients than in healthy individuals.
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PMID:Factor XII clotting activity and antigen levels in patients with thromboembolic disease. 145 Mar 22

beta 2-Glycoprotein I (apolipoprotein H), a constituent of normal human plasma, has been shown to inhibit the generation of amidolytic activity in plasma that has been exposed to negatively charged agents. Studies with purified Hageman factor (factor XII) demonstrate that this inhibitory property is directed against the activation of Hageman factor. In this study beta 2-glycoprotein I inhibited the kaolin-induced generation of clot-promoting properties in solutions of Hageman factor. This effect was localized to an interaction between beta 2-glycoprotein I and kaolin. In contrast, once Hageman factor was activated by kaolin, its clot-promoting properties were not inhibited by beta 2-glycoprotein I. Further, beta 2-glycoprotein inhibited the generation of amidolytic activity against H-D-prolyl-L-phenylalanyl-L-arginine p-nitroanilide dihydrochloride in mixtures of Hageman factor and ellagic acid. The specificity of the action of beta 2-glycoprotein I was confirmed by its neutralization by immunoglobulin fractions of antiserums directed against this protein.
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PMID:Inhibition of the activation of Hageman factor (factor XII) by beta 2-glycoprotein I. 336 Dec 30

Lupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-beta 2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of beta 2-glycoprotein I. Based on these observations, the effect of anti-beta 2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-beta 2-glycoprotein I. The dose-response curve of anti-beta 2-glycoprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor XIIa activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of beta 2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of beta 2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of beta 2-glycoprotein I was independent of the inhibition caused by the anti-beta 2-glycoprotein I/beta 2 glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-beta 2-GP-I/beta 2-GP-I complex. This complex may be a lupus anticoagulant.
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PMID:Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. 748 6

Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis and fetal loss. Two hundred eighty-nine patients with a history of recurrent spontaneous abortion were subjected to screening examinations for the etiology of these abortions. Endocrine abnormality (28.0%), uterine abnormality (10.4%), autoimmune diseases (1.4%), antiphospholipid antibody syndrome (4.5%), and balanced type chromosome translocation (4.2%) were found as underlying causes of recurrent abortions, and the remaining 55.0% of the 289 patients were classified as having an unexplained etiology. Congenital thrombophilia such as protein C (PC) deficiency, protein S (PS) deficiency, antithrombin deficiency, and factor V Leiden mutation was not frequently detected; only one patient had PS deficiency. A reduced factor XII activity was found at a frequency of 4.2%. The frequency of methylene tetrahydrofolate reductase gene C677T mutation in recurrent aborters (0.38) was the same as that found in a fertile control group. Although the prevalence of anti-beta2-glycoprotein I antibody (abeta2-GPI) syndrome was very low (1.7%), patients with a high titer of immunoglobulin G (IgG) class abeta2-GPI, despite anticoagulation therapy, experienced severe fetomaternal complications in subsequent pregnancies. The rate (13.8%) of positive tests for serum IgA class abeta2-GPI in patients with unexplained etiology was higher than that in the controls (0%) (P < .05). We conclude that congenital thrombophilia is rare in Japanese patients who had experienced consecutive spontaneous abortions.
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PMID:Recurrent pregnancy loss: etiology of thrombophilia. 1137 65

Forty female patients with either primary anti-phospholipid syndrome (n = 26) or systemic lupus erythematosus (anti-phospholipid syndrome positive) (n = 14) were investigated for levels of factor XII, the presence of lupus anticoagulant and antibodies to cardiolipin, beta 2-glycoprotein I and factor XII. Twenty-one patients had a history of recurrent fetal loss (> 2, mean = 2.6). Lupus anticoagulant positivity showed a weak association with recurrent fetal loss (odds ratio = 1.1). While there was no association between the presence of antibodies to cardiolipin or beta 2-glycoprotein I with recurrent fetal loss, antibodies to factor XII showed a strong and statistically significant association (odds ratio = 5.4, P = 0.025).
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PMID:Antibodies to factor XII and recurrent fetal loss in patients with the anti-phospholipid syndrome. 1138 Apr 30

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

beta2-glycoprotein I (beta2GPI) bears the epitope(s) for autoimmune anticardiolipin antibodies (aCL) frequently present in patients with antiphospholipid syndrome (APS). beta2GPI is involved in coagulation and fibrinolytic systems, including inhibition of contact activation. Coagulation factor XII is an initiator of intrinsic coagulation and also of intrinsic fibrinolysis. We investigated the effect of aCL (= anti-beta2GPI antibodies), regarding intrinsic fibrinolysis using autoimmune monoclonal anti-beta2GPI antibodies derived from a patient with APS or from an NZW/BXSB-F1 mouse. We developed a chromogenic assay system to determine intrinsic fibrinolytic activity. The reaction was activated by kaolin in the euglobulin fraction. Exogenous beta2GPI slightly suppressed intrinsic fibrinolytic activity of the euglobulin fraction from normal plasma. Human monoclonal anti-beta2GPI antibody (EY2C9) and mouse monoclonal anti-beta2GPI antibody (WBCAL-1) in the presence of beta2GPI decreased the activity. In this system, the suppression remained significant in the presence of an excess of exogenous activated factor XII. Euglobulin fractions from APS patients' plasma paralleled low activities of intrinsic fibrinolysis compared with those from healthy subjects. Our results suggest that beta2GPI and anti-beta2GPI antibodies suppress intrinsic fibrinolytic activities. This suppression was not only due to inhibition of factor XII activation but was also related to function of activated factor XII (XIIa). These phenomena partly explain the mechanisms of thrombosis in APS.
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PMID:Suppressed intrinsic fibrinolytic activity by monoclonal anti-beta-2 glycoprotein I autoantibodies: possible mechanism for thrombosis in patients with antiphospholipid syndrome. 1243 60

Antibodies to factor XII (FXIIabs) have been demonstrated in some patients with the anti-phospholipid syndrome (APS). The presence of these antibodies were shown to lead to statistically significantly reduced levels of FXII (p = 0.02). In an extension to this study forty female patients with either primary APS (n = 26) or systemic lupus erythematosus (APS positive) (n = 14) were investigated for levels of factor XII, the presence of lupus anticoagulant and antibodies to cardiolipin, beta 2-glycoprotein I and factor XII. Twenty one of the forty patients had a history of foetal loss (> 2, mean = 2.6). Lupus anticoagulant positivity showed a weak association with foetal loss (odds ratio = 1.1). While there was no association between the presence of antibodies to cardiolipin or beta 2-glycoprotein I with foetal loss, antibodies to factor XII showed a strong and statistically significant association (odds ratio = 5.4, p = 0.025).
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PMID:Antibodies to factor XII: a possible predictive marker for recurrent foetal loss. 1263 2

Management of recurrent pregnancy loss (RPL) is considered to be difficult, in part because of cunfusion between autoantibodies and coagulation disorders. Autoantibodies and coagulation are related; two groups of multicenter studies concerning autoantibodies and coagulation reported that factor XII deficiency, hypofibrinolysis, anti-phosphatidylethanolamine (aPE), anti-beta2-glycoprotein I, anti-annexin A5, and lupus anticoagulant (LA) were found to be frequent risk factors in RPL women. Therefore, discrimination of autoantibodies and coagulation is important in understanding RPL well. We propose three types of pathways regarding reproduction, which are different and independent: (1) Negatively charged-phospholipid related antibodies (anti-phosphatidylserine; aPS, anti-cardiolipin; aCL, lupus anticoagulant; LA, anti-annexin A5; aANX), (2) factor XII-aPE-fibrinolysis: suppression of fibrinolysis, (3) protein C-protein S-factor V: loss of inactivation against activated factor V. Women with RPL and infertility showed similar findings in terms of the above clinical tests. Available data, however, is not enough to conclude whether these are pathogenic to infertile women.
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PMID:Autoantibodies and coagulation in reproductive medicine. 2966 22