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)

beta 2-Glycoprotein I (beta 2-GPI), a plasma protein with in vitro anticoagulant properties, has been recognized to have an important role in the antiphospholipid syndrome (APS) as a cofactor and an (co)antigen in ELISA assays. Although beta 2-GPI levels were found to be increased in some patients with APS, the clinical value of measuring beta 2-GPI levels in APS is not known. Several reports have suggested that anti-beta 2-GPI antibodies may be a marker for the APS and might be more specific for the vascular complications of the APS than anticardiolipin antibodies. There have been major discoveries about phospholipid (PL) and antibody binding sites on beta 2-GPI, although more studies are needed. Reports of changes in cell membrane PL composition or exposure of other anionic molecules by apoptosis, cell activation and oxidative injury suggest mechanisms to explain beta 2-GPI binding and the generation of cryptic epitopes for aPL/anti-beta 2-GPI antibodies.
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PMID:beta 2-Glycoprotein I and anti-beta 2-glycoprotein I antibodies: where are we now? 944 84

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

We report the case of a woman who, at the age of 27, developed a cerebral arterial occlusion. The laboratory investigations showed an anti-human beta2-glycoprotein I antibody, but no other biological sign of antiphospholipid antibody syndrome or autoimmune disorders. The patient otherwise presented with diabetes and moderate obesity. The species specificity of anti-beta2-glycoprotein I antibodies probably explains the discrepancy between false negative results for antiphospholipid antibodies assayed by clotting and ELISA studies and positivity for anti-human beta2-glycoprotein I. Further studies will be important to evaluate the frequency of such antibodies, as well as their value as a risk factor for venous and arterial thrombosis, and their signification within the antiphospholipid antibody syndrome.
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PMID:Acute stroke in a young female with anti-human beta2-glycoprotein I antibodies. 951 47

A 36-year-old female with a history of recurrent pregnancy loss experienced sudden onset of disturbance in consciousness, with right hemiparesis and total aphasia. Computed tomography revealed a massive hemorrhage in the left frontal lobe, and angiography showed occlusion of the anterior two-thirds of the superior sagittal sinus. Laboratory investigations detected the presence of lupus anticoagulant, elevation of the anticardiolipin beta 2-glycoprotein I complex antibody level, and a decreased protein S activity level. There were no underlying conditions, such as connective tissue disorders, malignancies, infectious diseases, and drug-induced disorders, so the diagnosis was primary antiphospholipid syndrome. Primary antiphospholipid syndrome should be considered in the evaluation of patients with "idiopathic" or "primary" sinus and cerebral venous thrombosis.
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PMID:Superior sagittal sinus thrombosis associated with primary antiphospholipid syndrome--case report. 954 Mar 31

Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid syndrome (APS) were found by many investigators, but their results appeared contraversional. We studied clinical significance of antibodies to beta 2-glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL) and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI, respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS development as a whole, its separate clinical symptoms (venous and arterial thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more frequently in the sera positive by LA and aCL. It is interesting that we discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is clinically important for upgrading diagnosis of APS.
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PMID:[Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new laboratory marker of antiphospholipid syndrome]. 957 46

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

It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via beta2-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of beta2-GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of beta2-GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r = 0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, beta2-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of beta2-GPI to protein C and its phospholipid dependency were investigated. Beta2-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated in the presence of cardiolipin and beta2-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and beta2-GPI, whereas they did not in the absence of either beta2-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and beta2-GPI, leading to protein C dysfunction.
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PMID:Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system. 964 98

A 29-year-old woman was referred for abdominal pain. Results of tests for lupus anticoagulant and antibodies to phosphatidylserine and to beta2-glycoprotein I were positive, but the patient had no features of systemic lupus erythematosus (SLE). Abdominal ultrasonography showed a thickening of the gallbladder wall without cholelithiasis. A surgical procedure revealed necrotic areas of the gallbladder wall, and a cholecystectomy was performed. Histologic examination of the gallbladder showed multiple thrombi and no vasculitis. Despite full-dose heparin, the patient developed a catastrophic antiphospholipid syndrome (APS) and subsequently died. Among connective tissue disorders, acute acalculous cholecystitis has been reported in patients with polyarteritis nodosa and/or SLE. APS should be considered as a possible cause of acalculous cholecystitis.
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PMID:Acalculous ischemic gallbladder necrosis in the catastrophic antiphospholipid syndrome. 966 91

"Antiphospholipid" autoantibodies are associated with arterial and venous thrombosis, recurrent fetal loss, and thrombocytopenia. At present, the best-characterized antigenic target for these autoantibodies (or Abs) is the phospholipid-binding protein beta2-glycoprotein I (beta2GPI). These Abs bind beta2GPI only in the presence of negatively charged phospholipids or microtiter polystyrene plates that have been specially treated to give the surface a negative charge. To determine whether the binding of these Abs to beta2GPI on negatively charged surfaces is dependent on increased density or neo-epitopes formed as a consequence of a conformational change on beta2GPI, we generated mutants of beta2GPI by site-directed mutagenesis and assessed the binding characteristics of anti-beta2GPI Abs to these mutants. Our results demonstrate that mutant F307*, which spontaneously forms significant dimerization, is bound best by all the anti-beta2GPI Abs in an anti-beta2GPI ELISA using irradiated polystyrene microtiter plates. In addition, these Abs bound mutant F307* coated onto standard polystyrene microtiter wells in the absence of phospholipid, whereas there was minimal binding with wild-type and mutant F307*/C288A, which formed minimal dimerization. Affinity-purified anti-beta2GPI Abs from patients with the antiphospholipid syndrome demonstrated significantly higher binding affinity for mutant F307* in fluid phase than for wild-type or mutant F307*/C288A of beta2GPI. These results demonstrate that autoantibody binding to beta2GPI is intrinsically of low affinity and that the binding is dependent on the density of the Ag and not on neo-epitope formation.
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PMID:Anti-beta 2-glycoprotein I autoantibodies from patients with the "antiphospholipid" syndrome bind to beta 2-glycoprotein I with low affinity: dimerization of beta 2-glycoprotein I induces a significant increase in anti-beta 2-glycoprotein I antibody affinity. 971 77


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