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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In September 1991, an NIH workshop on molecular and biological aspects of antiphospholipid antibodies (aPL) identified questions for future studies: are the antibodies defined by the ELISA and by the lupus anticoagulant tests the same? Is aPL directly responsible for disease? What is the antigen? What drives the production of aPL? What is the role of beta 2-glycoprotein I? What accounts for patient heterogeneity? Can a satisfactory animal model be developed? The NIH workshop did not address important clinical questions, including those of pathogenesis and treatment. In 1994 many of these questions have at least partial answers. beta 2-glycoprotein I appears to be an obligatory component of the antigen, abnormal coagulation is the probable central pathogenic event and animal models now exist. There are still critical unknowns that define a future research agenda: the genetics of the aPL syndrome, the relationship of aPL to SLE and mechanisms of pathogenesis (including why clotting is episodic and what is the cellular or anatomical location of the initial injury). Despite a decade of clinical studies, risk prediction for defined patient groups is only now beginning to be studied. There are still almost no randomized, prospective, controlled treatment trials on any aspect of the syndrome nor are there definitive answers regarding which among antiplatelet, anticoagulant or antithrombin therapies is superior, what is the role of immunosuppressive therapy and what experimental therapies might be introduced. The molecular biology of the antigen-antibody interaction will soon be fully understood, then the cellular and the organism biology. Definitive treatment interventions may await this understanding but adequate therapies are available at this time to conduct important and effective prospective clinical trials.
Lupus 1994 Aug
PMID:Antiphospholipid antibody: future developments. 780 22

Antiphospholipid antibodies are a diverse group of immunoglobulins initially thought to have specificity to phospholipid epitopes. It is apparent that autoimmune anticardiolipin antibodies require a serum cofactor beta-2-glycoprotein I (beta 2GPI) for their binding to phospholipids. Lupus anticoagulant also may bind to phospholipids by beta 2GPI or by prothrombin. The description of binding to protein-phospholipid epitopes may explain several perplexing features of these antibodies both in vitro and in vivo. Antiphospholipid antibodies have a well-established association with clinical disease--in particular thrombosis, thrombocytopenia and recurrent fetal loss. The mechanism of the predisposition to thrombosis seen with these antibodies is poorly understood. It has been suggested that they may cause endothelial dysfunction by causing increased tissue factor expression, by inhibiting prostacyclin secretion or by inhibiting fibrinolysis. Various platelet-activating activities have also been described. The evidence that antiphospholipid antibodies promote thrombosis by effects on endothelium or platelets is inconclusive. Inhibition of protein C activation, or of activated protein C action, has been demonstrated in vitro. A poor correlation between thrombosis in vivo and these inhibitory effects has been found. Beta-2-glycoprotein I has been identified as a cofactor for binding to phospholipid by thrombogenic anticardiolipin antibodies. That beta 2GPI may be a natural anticoagulant of importance remains to be proved. Inhibition by antiphospholipid antibodies of this anticoagulant function could explain the propensity to thrombosis seen in association with these antibodies.
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PMID:Antiphospholipid antibodies and thrombosis. 784

Lupus anticoagulants are antibodies that inhibit phospholipid dependent coagulation reactions in vitro. These antibodies are of clinical interest because of their association with a variety of clinical manifestations characterized by microvascular thrombosis. Although these antibodies were originally thought to be directed at negatively charged phospholipid, recent studies have suggested that they may be directed at phospholipid-protein complexes. The effect of antibodies directed against beta 2-glycoprotein I (beta 2-GP I, apolipoprotein H) on phospholipid-dependent coagulation reactions has been studied. Polyclonal and monoclonal antibodies to beta 2-GP I were found to inhibit thrombin generation in a dose dependent manner. Inhibition of thrombin formation was due to specific interaction with beta 2-GP I. There was no evidence that inhibition was due to crossreactivity with other proteins involved in the prothrombinase complex. These findings document that antibodies directed against beta 2-GP I can have anticoagulant activity analogous to lupus anticoagulant activity and are consistent with the recent observation of such activity in lupus anticoagulant patient samples.
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PMID:Antibodies to beta 2-glycoprotein I inhibit phospholipid dependent coagulation reactions. 811 86

We investigated whether anticardiolipin antibody (aCL), which is common in patients with end-stage renal disease (ESRD), was dependent on beta 2-glycoprotein I (GPI), a cofactor of aCL. Lupus anticoagulant (LA) was identified in 13/39 hemodialysis (HD) patients. GPI-independent aCL was positive in 12/39 of this group, five of whom had both GPI-independent aCL and LA. Three of the 20 patients on symptomatic and supportive treatment other than HD had LA, but none of them were aCL positive. When GPI was added to the assay system to allow for GPI-dependent aCL measurement, the optical density (OD) readings of 10/12 HD patients decreased, thus proving that they were negative for aCL. In contrast, the OD readings of 6 control patients with systemic lupus erythematosus (SLE) increased markedly (3/6) or decreased slightly to moderately (3/6), however, within the limits of positive range, indicating GPI-dependent cCL positivity. These results suggested that LA and GPI-independent aCL were produced in ESRD patients, especially those on HD, possibly through mechanisms related to the hemodialysis membrane. However, the significance of GPI-independent aCL in this clinical setting, which may differ from the GPI-dependent aCL detected in SLE patients, as well as the possible participation of serum GPI in the production of aCL remain to be clarified.
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PMID:beta 2-Glycoprotein I-dependent and-independent anticardiolipin antibody in patients with end-stage renal disease. 830 48

Antiphospholipid antibodies were originally thought to bind negatively-charged (anionic) phospholipids. Current evidence suggest that the target antigen is considerably more complex and includes beta 2-glycoprotein I, a phospholipid-binding plasma protein. Our understanding of the pathophysiology of the antiphospholipid syndrome has increased exponentially with a number of studies into the interactions of antiphospholipid antibodies and beta 2-glycoprotein I.
Lupus 1996 Apr
PMID:The role of beta 2-glycoprotein I in the antiphospholipid syndrome. 874 29

'Antiphospholipid' (aPL) antibodies are of clinical importance because of their strong association with vascular thrombosis, recurrent pregnancy loss, thrombocytopenia and other clinical manifestations like livedo reticularis, chorea and cardiac valvular disease. While aPL antibodies have traditionally been thought to be directed against negatively-charged (anionic) phospholipids current evidence suggests that these autoantibodies recognise protein-phospholipid complexes or the proteins themselves. A number of candidate proteins have been investigated with the two most extensively researched being beta 2-glycoprotein I and prothrombin.
Lupus 1996 Apr
PMID:Immunology of antiphospholipid antibodies and their interaction with plasma proteins. 874 30

We investigated the clinical significance of IgG phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-beta 2-GPI antibodies by ELISA. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies show an unique form of SLE.
Lupus 1995 Dec
PMID:Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in systemic lupus erythematosus. 874 70

The binding capacity to cardiolipin and the functional affinity of affinity-purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been compared with those of individuals with malaria and acquired immunodeficiency syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the incorporation of increasing amounts of beta 2-glycoprotein I (beta 2GPI) into the assay, in contrast to that of patients with infectious diseases. In addition, there were significant reductions of functional affinity in autoimmune disease, but not in malaria or in AIDS. These results indicate that beta 2GPI requirement for binding to the target antigen varies inversely with functional affinity in autoimmune disease when beta 2GPI was present, and suggest that IgG aCL are more heterogeneous in this type of disorder than in patients with infectious disease.
Lupus 1995 Dec
PMID:Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease. 874 71

The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important.
Lupus 1996 Oct
PMID:Functional effects of anticardiolipin antibodies. 890 63

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.
Lupus 1996 Oct
PMID:Anti-beta 2-glycoprotein I antibody: specificity and clinical significance. 890 64


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