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-GPI is a single chain, 50 kd glycoprotein made up of 326 amino-acids, present in human plasma at concentrations of about 200 micrograms/ml. It has been shown to represent the "serum cofactor" important in determining the binding of aCL to phospholipids both in fluid and in solid phase assays. Its cofactor activity is demonstrable for aPL antibodies from patients with autoimmune but not with infectious diseases. It is immunogenic in heterospecific models, and immunization with beta 2-GPI seems to be able to induce the production not only of anti-beta 2-GPI but also of aPL antibodies. Most probably its binding to CL changes the configuration of phospholipids to a more immunogenic one. The various characteristics of beta 2-GPI are summarized in Table I. beta 2-GPI has been recognized as a natural anticoagulant protein, but its possible role in the pathogenesis of the APLS remains to be determined.
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PMID:The beta-2-glycoprotein I and antiphospholipid antibodies. 150 19

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.
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PMID:Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease. 874 71

To investigate the prevalence, significance, and specificity of IgG isotype anti-beta 2-Glycoprotein I antibodies (a-beta 2-GPI) in antiphospholipid syndrome (APS), we developed an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG-a-beta 2-GPI and tested sera from 61 patients with autoimmune disorders (AID), 39 patients with APS and 22 patients with systemic lupus erythematosus without APS, 139 patients with various infectious diseases (hepatitis C virus infection, human immunodeficiency virus infection, Q fever, Mediterranean spotted fever, syphilis) and 97 healthy control subjects. Using irradiated plates coated with human beta 2-GPI, we showed that in the sera of patients with AID, optical densities from the coated wells were significantly higher than those from the noncoated ones (p = 0.0001). In this assay, intra-assay and inter-assay variation coefficients ranged between 4% and 10%. Clinical evaluation showed that IgG-a-beta 2-GPI were found in 23 of 61 patients with AID but in only one patient with an infectious disease. The presence of the IgG-a-beta 2-GPI in association with APS (p = 0.005) was statistically significant with high specificity (98%) and positive predictive value (87.5%) but with low sensitivity (54%), and was significantly associated with venous thrombosis (p = 0.0025). In addition, the IgG-a-beta 2-GPI levels were highly correlated with those of anticardiolipin antibodies (aCL) (p < 0.001). In contrast to a-beta 2-GPI, aCL were found with a high prevalence (40%) in patients with infectious diseases. Because of their high specificity, anti-beta 2-GPI antibodies appear to be useful tools in the evaluation of the risk of APS. However, because of their low sensitivity, their detection needs to be associated with that of aCL.
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PMID:Prevalence and clinical significance of IgG isotype anti-beta 2-glycoprotein I antibodies in antiphospholipid syndrome: a comparative study with anticardiolipin antibodies. 914 46

Great progress has been made within the past 10 years in characterizing, assaying, and describing mechanism(s) of action in vitro of antiphospholipid antibodies (a-PL Abs); three prominent members are reagin, anticardiolipin antibodies (a-CL Abs), and the lupus anticoagulants (LAC). The major focus of this review is on basic and current biochemical and immunologic research. First, the biochemistry, structural composition, and sources of anionic and dipolar ionic (zwitterionic) phospholipids are discussed together with several serum antibodies directed to these phospholipids. Cardiolipin, the most acidic phospholipid (net negative charge of 2 at pH 7.0) has been historically important as an antigen for testing reagin in syphilis serology, and currently is part of the antigenic composition used in the Venereal Disease Research Laboratory (VDRL) tests. In this connection, the chronic biological false-positive test for syphilis and the LAC are discussed in association with autoimmune disorders such as systemic lupus erythematosus. Second, a naturally occurring plasma anticoagulant in vitro and a critical cofactor for binding of purified autoimmune a-CL Abs to cardiolipin is considered, the beta 2-glycoprotein I (beta 2-gpI). This single-chain plasma polypeptide is highly glycosylated, has 326 amino acids, a molecular weight of 50 kD, and is characterized by repeating amino acid motifs or domains that structurally resemble multiple loops. The highly cationic C-terminal fifth domain binds to anionic phospholipids. The beta 2-gpI is a member of the short consensus repeat superfamily of proteins, and is compared with other proteins with similar domains. Third, experiments are detailed for defining LAC and distinguishing it from other a-CL Abs. Cofactors are also associated with LAC and include beta 2-gpI, prothrombin, protein C, protein S, tissue factor, and factor XI. Thus, LAC antibodies are heterogeneous, and no individual assay can detect all LACs. Because patients with syphilis and other infectious diseases have no cofactor associated with a-CL Abs, their plasma LACs are negative. The a-CL Abs found in infection are not associated with the clinical features of the antiphospholipid syndrome. LAC assays are important because of the pathogenetic association with clinical observations of venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss. Finally, reports leading to development of currently used direct solid-phase enzyme-linked immunosorbent assays (ELISA) for testing a-PL Abs are outlined; these developments have greatly increased understanding of the basic immunology of target antigens and their respective antibodies. Of significance, a-CL Abs cross-react with other anionic phospholipids. Additionally, the results of these assays led to the realization that high levels of circulating a-PL Abs over long periods are associated with a number of clinical problems now known collectively as the antiphospholipid syndrome.
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PMID:Antiphospholipid antibodies: basic immunology and assays. 914 49

Male (NZW x BXSB)F1 (W/BF1) mice develop a systemic lupus-like syndrome characterized by thrombocytopenia, coronary vascular disease, nephritis, and anticardiolipin antibodies. Three stable hybridoma cell lines secreting monoclonal anticardiolipin antibodies were developed from these mice by fusing their splenic lymphocytes with nonsecreting myeloma cell line, NS-1. Monoclonal antibody A1.17 reacted with cardiolipin in a beta2-Glycoprotein I-dependent manner. The epitope for this antibody consisted of beta2-glycoprotein I bound to cardiolipin or immobilized on plastic plates. Other anionic phospholipid-binding proteins, such as prothrombin or annexin V, had no significant effect in the reactivity of these antibodies. The specificity is similar to the autoimmune anticardiolipin antibodies described in patients with systemic lupus erythematosus and other infectious diseases. In contrast, monoclonal antibodies A1.72 and A1.84 reacted with cardiolipin in the absence of beta2-glycoprotein I. Beta2-glycoprotein I, either in the fluid phase or bound to cardiolipin, inhibited the binding of these antibodies. The specificity of the latter two antibodies was similar to that described in patients with syphilis and allied disorders. Both types of antibodies had lupus anticoagulant properties. Thus lupus-prone male (NZW x BXSB)F1 (W/BF1) mice develop both beta2-glycoprotein I-dependent and beta2-glycoprotein I-independent anticardiolipin antibodies.
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PMID:Characterization of beta2-glycoprotein I-dependent and -independent "antiphospholipid" antibodies from lupus-prone NZW/BXSB F1 hybrid male mice. 932 49

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

Three antiphospholipid antibodies (aPLs), namely, antiphosphatidylinositol antibody (antiinositol antibody), antiphosphatidylserine antibody (antiserine antibody), and anticardiolipin. beta 2-glycoprotein I complex antibody (antiCL. beta 2-GPI antibody), were determined in 49 children with idiopathic thrombocytopenic purpura (ITP) consisting of 14 newly-diagnosed cases and 35 chronic cases. Determination of aPL was performed twice in the newly-diagnosed patients, once each during the acute and convalescent phases, and once in the chronic patients. The positive rates in the acute and convalescent phases of the newly-diagnosed group and in the chronic group were, respectively, 14.3%, 28.6%, and 18.8% for the antiinositol antibody, 14.3%, 14.3%, and 15.6% for the antiserine antibody, and 21.4%, 28.6%, and 25.0% for either of these 2 antibodies. Thus, antiinositol and antiserine aPLs were present at high incidences; however, all patients were negative for the antiCL. beta 2-GPI antibody. No correlation was noted between either the antiinositol or the antiserine antibody and peripheral platelet count, anti-GP IIb/IIIa antibody or PAIgG. Thus, although some aPLs are present in both acute and chronic pediatric ITP, the aPLs seems to be of an infectious disease type. No results that suggest possible involvement of aPLs in ITP pathology were obtained.
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PMID:[Antiphospholipid antibodies in children with idiopathic thrombocytopenic purpura]. 1241 85

The anticardiolipin (aCL) antibody test was first established in 1983, using cardiolipin (negatively charged phospholipid) as an antigen in a solid-phase immunoassAy. It was first applied to the study of systemic lupus erythematosus patients, and was found associated with thromboses and recurrent pregnancy losses. The wide use of this test was determinant in the definition of the "aCL or antiphospholipid syndrome" (APS).Later, it was demonstrated that aCL antibodies do not recognize anionic phospholipids but are directed against plasma proteins bound to anionic phospholipids, mainly beta-2-glycoprotein I, which is now considered as the autoantigen in APS. Anti-beta-2-glycoprotein I (anti-beta2GPI) is not yet accepted as a serological criterion for APS, but most investigators would consider a patient with anti-beta2GPI antibodies and clinical features of APS to have the syndrome. aCL and anti-beta2GPI are a heterogeneous group of antibodies with different clinical significances and can be present in different autoimmune diseases as well as in infectious diseases.
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PMID:Anticardiolipin and anti-beta-2-glycoprotein I antibodies. 1580 3