Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiphospholipid antibodies (aPL) present in autoimmune disorders are associated with thromboembolic episodes, and their binding to phospholipids (PL) is mediated by a plasma cofactor, beta 2-glycoprotein I (beta 2GPI). Both PL and beta 2GPI seem necessary for binding, thus indicating that the two components comprise the epitope against which aPL are directed. Using an anti-beta 2GPI antibody ELISA with the antigen adsorbed onto polyvinylchloride (PVC) plates, we detected high antibody titres in 12 out of 12 plasma from patients with the antiphospholipid syndrome. No or very low positivity was obtained when the same ELISA was carried out in polystyrene (PST) plates, while an increasing positivity was found when processed (i.e. more hydrophilic) or COOH-surface PST plates were used. When beta 2GPI dependent IgG-aPL were purified using agarose-immobilized cardiolipin, 4 out of 4 preparations were highly positive in anti-beta 2GPI antibody ELISA using PVC plates, while beta 2GPI was not fully recognized by aPL-IgG when adsorbed onto PST plates. These findings demonstrate that aPL are, in fact, anti-beta 2GPI antibodies directed against a cryptic epitope which is expressed when beta 2GPI is bound to anionic phospholipid, or another suitable surface.
 ...
PMID:Autoimmune antiphospholipid antibodies are directed against a cryptic epitope expressed when beta 2-glycoprotein I is bound to a suitable surface. 753 19

We conducted this study to investigate whether antioxidized low-density lipoprotein (a-oxLDL) is an antibody to cryptic and/or neo-antigen on beta2-glycoprotein I (GPI), which is introduced by binding to anionic phospholipid, similar to that of GPI-dependent anticardiolipin antibody (aCL) employing a-oxLDL ELISA. We found that no significant optical density differences existed among systemic lupus erythematosus patients, including cases with aCL and/or lupus anticoagulant positivity, before and after the addition of GPI. Our results suggest that a-oxLDL is not an antibody to denatured GPI, but rather to oxLDL.
 ...
PMID:Negligible synergistic effect of beta2-glycoprotein I on the reactivity of antioxidized low-density lipoprotein antibody to oxidized low-density lipoprotein. 863 31

There is accumulating evidence that anti-phospholipid (aPL) antibodies in the sera of patients with autoimmune diseases bind to a complex of anionic phospholipids and plasma phospholipid-binding proteins, namely beta 2-glycoprotein I (beta 2-GPI) and prothrombin. It has been suggested that a conformational change in beta 2-GPI, induced by binding either to anionic phospholipids or to the oxygen molecules on the irradiated microtiter plate, reveals cryptic antigenic epitope(s) in the native protein. We used an enzyme-linked immunoassay for measuring antibodies against two phospholipid-binding proteins, i.e., beta 2-GPI and prothrombin, absorbed to an irradiated plate in an unselected series of 139 patients with systemic lupus erythematosus (SLE). Elevated levels of antibodies against beta 2-GPI were found in 49% of patients and antibodies against prothrombin in 34% of patients. Both antibodies were significantly associated with deep venous thrombosis in patients with SLE (P = 0.009 for both antibodies). Accordingly, testing of these antibodies seems to be clinically useful in evaluating the risk of thrombosis.
 ...
PMID:Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus. 867 35

Cardiolipin binding of IgG-class anticardiolipin antibody (aCL) depends on the existence of beta 2-glycoprotein I (beta 2-GPI). We developed an EIA system that enables detection of antibodies against beta 2-GPI, without the presence of cardiolipin. This system involves use of irradiated polystyrene plates, in which oxygen atoms are introduced onto the surfaces of the plates. beta 2-GPI bound to the surface of these plates is assumed to undergo a conformational change that exposes normally cryptic epitopes. Anti-beta 2-GPI antibody measured using this EIA system showed good correlation with aCL measured by conventional EIA methods and may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE. Utilizing this EIA system and beta 2-GPI-deleted mutants, we found that the fourth domain of beta 2-GPI is involved in expression of one of the cryptic epitopes recognized by aCL. We also found that oxidized LDL are sequentially targeted by beta 2-GPI and aCL.
 ...
PMID:Anti-beta 2-glycoprotein I antibody: specificity and clinical significance. 890 64

The family of antiphospholipid antibodies includes antibodies binding to cardiolipin in serological test for syphilis, antibodies prolonging the clotting time in lupus anticoagulant test, antibodies reacting with plasma phospholipid-binding proteins, such as beta 2-glycoprotein I and prothrombin, and antibodies binding to oxidized low-density lipoprotein (LDL). Antiphospholipid antibodies are traditionally associated with arterial and venous thrombosis in patients with primary or secondary antiphospholipid syndrome. The recent studies, especially those on patients with myocardial infarction, extend the concept of antiphospholipid antibodies, and suggest that they play a role also in atherosclerosis. Based on the clinical studies and immunological findings, it seems that the differences in the specificity of antiphospholipid antibodies may reflect to their pathogenetic mechanisms and, finally, to their clinical consequences. The present review suggests that antibodies to oxidized LDL may not interfere directly with blood coagulation, but seem to have importance in the inflammation of the vessel wall in atherosclerosis and in vasculitis. Instead, antibodies to beta 2-glycoprotein I and to prothrombin show a closer association with thrombosis. It is possible that in the atherosclerotic plaque, the plasma proteins, such as beta 2-glycoprotein I or prothrombin, are bound to the endothelial surface and antibodies to cryptic epitopes revealed in these proteins are induced. These antibodies may contribute to the formation of atherosclerotic thrombosis by changing the balance of haemostasis toward hypercoagulative state.
 ...
PMID:Antiphospholipid antibodies and atherosclerosis. 890 78

During late seventies it became apparent that the appearance of antiphospholipid antibodies is associated with thromboembolic manifestations, such as cerebral or myocardial infarction, pulmonary thromboembolism, deep vein thrombosis, intrauterine fetal losses and thrombocytopenia. The term antiphospholipid syndrome has been used to define this set of pathologic features. Recognition of this syndrome has spread worldwide as its clinical implications have become appreciated. Recent studies showed that cofactor, beta 2-glycoprotein I (beta 2-GPI) is required for binding of anticardiolipin antibodies (aCL) raised in the patients with SLE and related other autoimmune disorders. However, this finding has generated considerable controversy. Four different hypotheses have been proposed to explain the specificity of aCL: (1) CL is directly recognized by aCL; (2) the beta 2-GPI-CL complex is the structure recognized by aCL; (3) the beta 2-GPI is the actual target antigen for aCL but is cryptic in the absence of CL; and (4) the actual epitope for aCL appears on the native structure of beta 2-GPI. We showed that aCL bound to beta 2-GPI interacting with poly-oxygenated plates and in the absence of CL, an interaction which depends on introduction of oxygen atoms on the polystyrene surface. We also showed that the beta 2-GPI bound to CL via a particular region on the fifth domain, namely C281KNKEKKC288, and the tertiary structure of the region is involved in binding to phospholipid. Several mechanisms to explain the vascular injury and thrombosis associated with aCL have been proposed, primarily based on their phospholipid reactivity to activated platelets. Whether aCL-through binding to complex of beta 2-GPI and negatively charged phospholipid in the phospholipid-dependent coagulation reactions of hemostasis contribute to the increased risk of thrombosis in patients with aCL is an important question in need of an answer. We have demonstrated the possibility that not only activated platelets but also oxidized lipoproteins, e.g., low-density lipoprotein (LDL), may be thrombogenic targets of aCL which recognize the altered beta 2-GPI structure.
 ...
PMID:[Autoantibodies and thrombosis]. 936 65

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.
 ...
PMID:beta 2-Glycoprotein I and anti-beta 2-glycoprotein I antibodies: where are we now? 944 84

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.
 ...
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

Anticardiolipin antibodies (aCL) found in sera from patients with antiphospholipid syndrome recognize a cryptic epitope that appears on the beta2-glycoprotein I (beta2-GPI) molecule when beta2-GPI interacts with a lipid membrane composed of negatively charged phospholipid or when beta2-GPI is adsorbed on a polyoxygenated polystyrene plate. A homology based model of beta2-GPI was constructed based on the NMR coordinates of sushi domains of human factor H. The conformation was like a cylinder consisting of five domains, its IV and V domains being glued by electrostatic interaction. We used phage-displayed random peptide libraries to search the epitopes of human aCL. Structures similar to consensus sequences selected by a biopanning method was found on domain IV of beta2-GPI.
 ...
PMID:Epitopes on beta2-GPI recognized by anticardiolipin antibodies. 981 65

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.
 ...
PMID:Binding properties of antibodies to prothrombin and beta2-glycoprotein I (beta2-GPI) assayed by ELISA and dot blot. 1059 71


1 2 Next >>