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)

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

Most anti-phospholipid antibodies (aPL) associated with the anti-phospholipid syndrome are autoantibodies with specificity towards beta2-GPI (anti-beta2-GPI) or prothrombin (anti-II). They are mainly screened by ELISA using polyoxygenated plates. However, some authors have claimed that immunoblotting can also be used. Exposure of cryptic epitopes or increase of antigen density on its binding to either phospholipids or suitable plastic surfaces are the two hypotheses proposed for the interaction of beta2-GPI or prothrombin with their antibodies. Forty-five patients with aPL were studied: 25 with lupus anti-coagulant (LA) and anti-cardiolipin antibodies (aCL), 10 with LA alone and 10 with aCL but negative LA. All patients with LA and aCL were positive for anti-beta2-GPI by ELISA and dot blot, while 15/25 had anti-IIELISA and 14 of them also had anti-II by dot blot assay. No patient with LA alone tested positive for anti-beta2-GPI by ELISA or dot blot, whereas 6/10 had anti-IIELISA (five of them were also positive by dot blot). Four out of 10 aCL-positive patients had anti-beta2-GPI by ELISA and dot blot, while none of this group had anti-II by ELISA or dot blot. Antibody binding to beta2-GPI or prothrombin in both ELISA and dot blot was significantly reduced by phospholipid liposomes mixed together with beta2-GPI or prothrombin, whereas liposomal eluants retained it in both assays. Parallel fluid-phase inhibition experiments using increasing concentrations (up to 200 microg/ml) of beta2-GPI or prothrombin demonstrated that antibody binding reduction was more evident on dot blot than on ELISA. It was almost completely abolished on dot blot, while on ELISA a moderate inhibition was achieved even at the highest protein concentration. However, antibody binding on ELISA was virtually abolished when diluted sera were incubated with high protein concentrations applied to nitrocellulose membranes. We could infer that ELISA and dot blot detect antibodies with some differences in avidity but directed against native epitopes on beta2-GPI and prothrombin.
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PMID:Binding properties of antibodies to prothrombin and beta2-glycoprotein I (beta2-GPI) assayed by ELISA and dot blot. 1059 71

New evidence indicates that antibodies to beta2-glycoprotein I (anti-beta2GPI) or to human prothrombin (anti-II)(or to both of these) are specific markers of the antiphospholipid syndrome (APS). They have been mainly associated with thrombotic complications in patients with APS. However, some studies have reported that elevated levels of anti-II, but not of anfi-beta2GPI, imply a risk of venous thrombosis (VT) or arterial thrombosis (AT) in subjects with no previous thrombosis and no antiphospholipid antibodies (aPL) by ELISA. The present study Included 180 patients with a history of thrombosis, 83 of them without aPL (group I) and the remaining 97 diagnosed as having APS (group II). Anti-beta2GPI was found in only 1 of the 83 patients from group I but was found in approximately 50% of those from group II (P < .0001). In contrast, positive anti-II was detected with a high prevalence in patients from group I (VT, 22.6%; AT, 26.7%) and in those from group II (VT, 37.5%; AT, 14.6%). No statistical differences were found in the prevalence of anti-II between the two groups of patients. On the other hand, such a difference was significant when compared with results in a normal group (1/67, 1.4%, P < .0001). These data Indicate that anti-II occurs frequently in patients with previous thrombosis either with or without lupus anticoagulant activity. Accordingly, testing of anti-II might be clinically useful in the evaluation for thrombophilla.
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PMID:Occurrence of anti-prothrombin and anti-beta2-glycoprotein I antibodies in patients with history of thrombosis. 1059 89

Antiphospholipid antibodies (aPL) have been associated with clinical conditions that involve arterial or venous thrombotic events and pregnancy morbidity including fetal loss and preeclampsia. These antibodies are detected by various functional tests for the lupus anticoagulant, the anticardiolipin ELISA, the anti-beta2-glycoprotein I ELISA, or ELISA tests for other aPL. The pathogenic mechanisms are poorly understood. A "2 hit" hypothesis has been entertained in which there is underlying vascular (endothelial) damage, and in the presence of an aPL, a thrombotic complication emerges. Although the role of immunologic processes and autoimmunity appears important, immunosuppressive therapy has not proven very effective. Treatment options are limited to antiplatelet therapy (primarily for arterial events) and anticoagulation (with coumadin, heparin, or low molecular weight heparins) because of lack of understanding of the inciting factors and the pathogenesis of the process.
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PMID:The antiphospholipid syndrome: immunologic and clinical aspects. Clinical spectrum and treatment. 1078 52

The antiphospholipid syndrome(APS) is characterized by predominant clinical features of venous and arterial thrombosis and recurrent pregnancy loss accompanied by antiphospholipid antibodies(aPL) such as anticardiolipin antibodies(aCL) and lupus anticoagulant(LA). In 1990, three individual research groups, including us, first reported that a 50 kD plasma cofactor is required for the binding of aCL to cardiolipin(CL) and now, beta 2-glycoprotein I(beta 2-GPI), which binds to anionic phospholipids(PLs), is widely believed to be the major antigen for aCL. It was also reported that epitopes for such aCL are cryptic and that they appear only when beta 2-GPI interacts with lipid membranes containing anionic PLs, such as CL and phosphatidylserine, or with a polyoxygenated polystyrene surface. In contrast, prothrombin was recently identified as the "true" antigen for LA. In this review paper, we would like to describe on specificity of aPL and also on a possible mechanism on autoantibody-dependent development of atherosclerosis.
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PMID:[Assay principles of antiphospholipid antibodies and heterogeneity of the antibodies]. 1081 Aug 76

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

We report a case of acute adrenal insufficiency in a context of probable bilateral adrenal haemorrhage, as revealed by CT-scan in a 52-year-old woman with a history of spontaneous abortion and repeated ischaemic stroke without symptoms or signs of collagen vascular disease. The symptoms began after the patient had successfully been treated for pneumonia. She had persistently high titres of IgG anticardiolipin antibodies, antibodies against beta 2-glycoprotein I and a lupus anticoagulant. The diagnosis of primary antiphospholipid syndrome with adrenal insufficiency was postulated.
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PMID:[Bilateral adrenal hemorrhage with adrenal insufficiency in the framework of primary antiphospholipid antibody syndrome]. 1082

We examined the role of autoantibodies to beta2-GPI and prothrombin (PT) in the inhibition of annexin V binding to cardiolipin (CL) and the association with clinical manifestations of the anti-phospholipid syndrome (APS). Plasma samples from 59 patients with anti-phospholipid (aPL) antibodies were studied. Affinity purification of total IgG and IgG anti-ss2-GPI antibodies was performed using staphylococcal protein A and phospholipid liposomes. Annexin V binding to CL was significantly inhibited by 31/59 (53%) aPL+ plasma samples. There was a significant association between annexin V inhibition and elevated levels of IgG anti-cardiolipin (aCL) (r = -0.62; P < 0.001), IgG anti-ss2-GPI (r = -0.67; P < 0. 001) and a weaker association with lupus anti-coagulant (r = -0.27; P = 0.05). There was no association with other isotypes of aCL and anti-ss2-GPI or with anti-PT of any isotype. In patients with clinical manifestations of the APS there were higher levels of IgG aCL (median (range) Z score): 10.0 (0-17.6) versus 5.0 (0-16.1); P = 0.03), IgG anti-ss2-GPI (4.5 (0-11.3) versus 0.9 (0-9.7); P = 0.02) and greater inhibition of annexin V binding to CL (-3.4 (-11.4-0.6) versus -1.1 (-10.8-1.2); P = 0.22). Odds ratios for the laboratory assays and the presence of clinical manifestations of the APS varied between 0.38 and 4.16, with the highest values for IgG aCL (4.16), IgG anti-ss2-GPI (3.28) and annexin V inhibition (2.85). Additional experiments with affinity-purified IgG antibodies indicated that inhibition of annexin V binding was dependent upon the concentration of ss2-GPI and anti-ss2-GPI antibodies. These results indicate that inhibition of annexin V binding to procoagulant phospholipid surfaces is dependent upon anti-ss2-GPI antibodies and suggest a role for annexin V in the pathogenesis of the APS.
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PMID:Anti-beta2-glycoprotein I (GPI) autoantibodies, annexin V binding and the anti-phospholipid syndrome. 1084 35

The precise mechanism of interaction between autoantibodies and beta2-glycoprotein I (beta2GPI) and the experimental conditions to be used for their detection are still under debate. Until now, these interactions have been studied under static conditions. We have investigated the interactions of purified IgG from 25 lupus anticoagulant-positive patients with immobilized beta2GPI under flow conditions by real-time analysis based on surface plasmon resonance technology. Sensor chips were coated with purified human beta2GPI coupled to dextran via amino groups at low densities (1.4, 1.8 or 2. 4 ng beta2GPI/mm2). Four patients' IgG displayed efficient binding and had the highest so-called antiphospholipid IgG levels by enzyme-linked immunosorbent assay (ELISA) and the highest absorbance values in an anti- beta2GPI ELISA at a beta2GPI density reported to be around 12 ng/mm2. Binding of antibodies to the beta2GPI sensor chips proved to be dependent upon the IgG concentration and beta2GPI density and was inhibited by a rabbit antibody against beta2GPI. Similar association and dissociation profiles were observed for the four efficient binders. The fast rate of dissociation limited the binding of autoantibodies to beta2GPI and was highly suggestive of a monovalent association, confirmed by binding of Fab fragments under similar experimental conditions. In conclusion, monovalent binding of low-affinity antibodies to beta2GPI immobilized at a density as low as 1.8 ng/mm2 could be detected using surface plasmon resonance.
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PMID:Monovalent binding of autoantibodies to beta2-glycoprotein I, detected using surface plasmon resonance at low antigen density. 1084 99

The clinically relevant antiphospholipid antibodies (APA) include anticardiolipin antibodies and lupus anticoagulant. Most autoimmune APA require the presence of a cofactor for phospholipid binding, and the growing list of candidate cofactors has prompted redefinition of APA to 'antiphospholipid protein antibodies'. Current evidence favours beta2-glycoprotein I (beta2GPI) and prothrombin as the primary antigens for anticardiolipin antibodies and lupus anticoagulant respectively. Patients with APA show a predisposition for venous and arterial thromboembolism, recurrent fetal loss, thrombocytopenia and a number of neurological syndromes and miscellaneous conditions. The association between APA and thrombosis has been well documented, but a definite mechanism remains to be clarified. Proposed mechanisms have included disruption of endothelial regulatory processes, impairment of fibrinolysis, augmented platelet activation and/or adhesion, inhibition of antithrombin activity and negation of the anticoagulant effects of beta2GPI and annexin V. In this review we describe recent insights into the role of beta2GPI as a natural anticoagulant, the procoagulant effects of APA on the Protein C system, the interactions between APA and prothrombin resulting in augmentation of thrombin generation, and cellular expression of Tissue Factor in patients with APA. Cellular immunity to beta2GPI is also discussed. Elucidation of these pathophysiological mechanisms may shed further light on the association between APA and thrombosis.
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PMID:Recent insights into antiphospholipid antibody-mediated thrombosis. 1085 78


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