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)

The lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are clinically relevant because of their association with thrombosis and pregnancy loss. The group of antiphospholipid antibodies (aPL) includes antibodies primarily directed against various phospholipid-binding proteins, mainly beta2-glycoprotein I (beta2GPI) and prothrombin. Some studies suggest that there is an association between the presence of anti beta2GPI antibodies (alphabeta2GPI) of IgG isotype and thrombosis. Therefore, aPL defined according to the plasma protein to which they are directed appear to be more appropriate for the evaluation of their clinical importance. Using home-made ELISAs we evaluated the presence of alphabeta2GPI and antiprothrombin antibodies (anti-II) of both isotypes (IgG and IgM) in a group of 233 patients with LA and/or aCL. Forty-four women had a history of pregnancy loss, 45 patients had a history of venous thrombosis (VT) and 32 of arterial thrombosis (AT). Patients from the autoimmune group (systemic lupus erythematosus and antiphospholipid syndrome) had a higher prevalence of alphabeta2GPI and/or anti-II than those from the miscellaneous group. In the univariate analysis, a significant association was shown between the presence of alphabeta2GPI-IgG (OR 3.2; 95% CI 1.5-6.6) and previous VT, but not AT. Anti-II were related to VT but the multivariate analysis showed that alphabeta2GPI-IgG are the only independent risk factor for VT (OR 3.0; 95% CI 1.3-6.2). The presence of alphabeta2GPI-IgM correlates well with a history of pregnancy loss (OR 2.6; 95% CI 1.1-6.1). The coagulation tests profile showed that the clotting assays were more prolonged in patients having aCL, alphabeta2GPI or anti-II. But a higher prevalence of abnormal results was only found for the dilute Russell viper venom time in patients with VT, as compared to those without thrombosis (94.4% vs. 58.7%, p <0.02). The measurement of alphabeta2GPI of both isotypes could help to identify aPL-positive patients with a higher risk for thrombosis and pregnancy loss, although this association should be confirmed by prospective studies.
Thromb Haemost 1997 Sep
PMID:Relationship of anti beta2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies. 930 45

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.
Hokkaido Igaku Zasshi 1997 Sep
PMID:[Autoantibodies and thrombosis]. 936 65

The prevalence and clinical significance of anti-oxidized low-density lipoprotein antibodies (anti-ox-LDL) were evaluated in patients with the antiphospholipid syndrome (APS). Anti-ox-LDL were measured in the sera of 107 patients with APS (64 primary APS, 43 secondary to systemic lupus erythematosus) by enzyme-linked immunosorbent assay (ELISA) utilizing malondialdehyde (MDA)-modified LDL as antigen. In the same patients, anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein I antibodies (anti-beta2GPI) were also measured. A positive titre of anti-ox-LDL was detected in 22% of patients, but only in 6% of control subjects (chi2 = 12, P = 0.0005). Levels of anti-ox-LDL were higher in patients with arterial thrombosis (n = 58) than in those without (n = 49) (P = 0.0001). Anti-ox-LDL levels correlated weakly with those of aCL (r = 0.196, P = 0.043), but not with those of anti-beta2GPI (r = 0.076). Our findings suggest that elevated levels of anti-ox-LDL may represent another potential marker of APS, particularly of patients prone to arterial thrombosis.
Br J Rheumatol 1997 Sep
PMID:Autoantibodies against oxidized low-density lipoprotein in antiphospholipid syndrome. 937 92

The antiphospholipid syndrome is a thrombophilic condition marked by antibodies that recognize anionic phospholipid-protein cofactor complexes. We recently reported that exposure to IgG fractions from antiphospholipid patients reduces the level of annexin-V, a phospholipid-binding anticoagulant protein, on cultured trophoblasts and endothelial cells and accelerates coagulation of plasma exposed to these cells. Therefore, we asked whether antiphospholipid antibodies might directly reduce annexin-V binding to noncellular phospholipid substrates. Using ellipsometry, we found that antiphospholipid IgGs reduce the quantity of annexin-V bound to phospholipid bilayers; this reduction is dependent on the presence of beta2-glycoprotein I. Also, exposure to plasmas containing antiphospholipid antibodies reduces annexin-V binding to phosphatidyl serine-coated microtiter plates, frozen thawed washed platelets, activated partial thromboplastin time (aPTT) reagent and prothrombin time reagent and reduces the anticoagulant effect of the protein. These studies show that antiphospholipid antibodies interfere with the binding of annexin-V to anionic phospholipid and with its anticoagulant activity. This acceleration of coagulation, due to reduced binding of annexin V, stands in marked contrast to the "lupus anticoagulant effect" previously described in these patients. These results are the first direct demonstration of the displacement of annexin-V and the consequent acceleration of coagulation on noncellular phospholipid surfaces by antiphospholipid antibodies.
Blood 1998 Sep 01
PMID:Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a "lupus procoagulant" phenomenon. 971 93

Screening of serum by using a surface plasmon resonance analysis assay identified beta2-glycoprotein-I/apolipoprotein H as a plasma component binding to the renal epithelial endocytic receptor megalin. A calcium-dependent megalin-mediated beta2-glycoprotein-I endocytosis was subsequently demonstrated by ligand blotting of rabbit renal cortex and uptake analysis in megalin-expressing cells. Immunohistochemical and immunoelectron microscopic examination of kidneys and the presence of high concentrations of beta2-glycoprotein-I in urine of mice with disrupted megalin gene established that megalin is the renal clearance receptor for beta2-glycoprotein-I. A significant increase in functional affinity for purified megalin was observed when beta2-glycoprotein-I was bound to the acidic phospholipids, phosphatidylserine and cardiolipin. The binding of beta2-glycoprotein-I and beta2-glycoprotein-I- phospholipid complexes to megalin was completely blocked by receptor-associated protein. In conclusion, we have demonstrated a novel receptor recognition feature of beta2-glycoprotein-I. In addition to explaining the high urinary excretion of beta2-glycoprotein-I in patients with renal tubule failure, the data provide molecular evidence for the suggested function of beta2-glycoprotein-I as a linking molecule mediating cellular recognition of phosphatidylserine-exposing particles.
J Clin Invest 1998 Sep 01
PMID:beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin. 972 58

Antiphospholipid antibodies associated with the antiphospholipid syndrome (APS) have been shown to bind plasma proteins, particularly beta 2-glycoprotein I (beta2-GPI). In this study the incidence of antibodies to solid-phase prothrombin was examined in patients with antiphospholipid syndrome and a variety of other inflammatory disorders. Significantly elevated levels of IgG anti-prothrombin (anti-PT) antibodies were detected in 63% of patients with APS (n = 27, median 22 arbitrary units: AU), 33% with SLE (n = 92, median 14 AU). 45% with rheumatoid factor (n = 22, median 16 AU), 21% with carotid artery stenosis (n = 21, median 15 AU), 32% with stroke (n = 38, median 13 AU). 67% of patients with a false positive serology for syphilis (n = 21, median 24 AU), 37% with HIV (n = 30, median 14 AU), 29% with syphilis (n = 14, median 19 AU) and 3% with infectious mononucleosis (n= 30, median 9 AU). In addition, a group of lupus anticoagulant (LA) positive patients (n = 48) was examined for antibodies to prothrombin, beta2-GPI and cardiolipin. 10 (21%) patients had raised levels of IgG anti-PT antibodies, 30 (62%) had significantly elevated levels of anti-beta2-GPI antibodies and 15 (31%) had elevated levels of anticardiolipin antibodies (ACA). Of the LA-positive patients, 15 (43%) were identified with definite APS, eight (23%) with probable APS, two (6%) with possible APS and 10 (28%) patients had no clinical evidence of APS. In conclusion, antibodies to prothrombin were found in a variety of inflammatory disorders and were therefore not specific for the APS. However, identification of the plasma proteins recognized by antibodies from patients with APS may provide insight into the pathogenic mechanisms involved in the heterogenous clinical manifestations of the APS.
Br J Haematol 1998 Sep
PMID:Antibodies to prothrombin in antiphospholipid syndrome and inflammatory disorders. 973 36

Anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) have been detected in patients with hepatitis C virus (HCV) infection and have been associated in autoimmune diseases (i.e. systemic lupus erythematosus) with an increased risk of thromboembolic events. Because of the high prevalence of HCV infection and the thrombotic risk described in thalassaemia we decided to investigate the prevalence of ACA and LA in a cohort of 68 thalassaemia patients. We found a high prevalence (34%) of beta2-glycoprotein I independent ACA in our thalassaemia patients which was related to HCV infection. None of patients developed any complications related to antiphospholipid antibodies (APL); therefore the clinical significance of positivity for APL in patients with HCV infection is at present unclear. In conclusion, the results of our study indicate that ACA in the serum of HCV-infected thalassaemic patients exhibit the characteristics of natural autoantibodies rather than those of the pathogenic autoantibodies that are found in patients with systemic lupus erythematosus.
Br J Haematol 1998 Sep
PMID:Lupus anticoagulant, anticardiolipin antibodies and hepatitis C virus infection in thalassaemia. 973 37

Most anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on beta2-glycoprotein I (beta2GPI). Despite a good correlation between standard ACA assays and those using purified human beta2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-beta2GPI antibodies. To characterize their reactivity profiles, human and bovine beta2GPI were immobilized on gamma-irradiated plates (beta2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/beta2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human beta2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine beta2GPI only (group I) or to bovine and human beta2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when beta2GPI was immobilized on gamma-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of beta2GPI density, as assessed using 125I-beta2GPI); (ii) and low avidity binding to fluid-phase beta2GPI (Kd in the range 10(-5) M). In contrast, all six group II samples showed (i) ability to bind human and bovine beta2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native beta2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/beta2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine beta2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of beta2GPI greatly influences its recognition by anti-beta2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.
Thromb Haemost 1998 Sep
PMID:Heterogeneity and immunochemical properties of anti-beta2-glycoprotein I autoantibodies. 975 16

Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared.
QJM 1998 Sep
PMID:Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome. 1002 16

The aim of this study was to evaluate the prevalence of IgG, IgA and IgM anti-beta2-GPI antibodies in anti-phospholipid syndrome (APS), and to establish the clinical significance of IgA type antibodies compared with the other isotypes. Anti-beta2-GPI antibodies were measured in the sera of 70 patients by solid-phase enzyme immunoassay in gamma-irradiated polystyrene plates coated with human purified beta2-GPI. Thirty-three out of the 70 patients were classified as having APS: three of them had primary, and 30 had secondary APS related to systemic lupus erythematosus (SLE). The remaining 37 patients had SLE without APS. Anti-beta2-GPI antibodies of IgG, IgA and IgM isotypes were present in 84.8%, 59.3% and 51.5% of patients with APS. Both the frequency and the level of each isotype were significantly higher in patients with APS. This association was very strong for IgA (P = 0.0004 for the antibody frequency and P < 0.0001 for the antibody level), as well as for IgG type antibodies (P < 0.0001 and P < 0.0001), whereas it was weaker for IgM (P = 0.01 and P = 0.04). A strong relationship was demonstrated between increased IgA anti-beta2-GPI antibody levels and a history of venous thrombosis, thrombocytopenia, heart valve disease, livedo reticularis and epilepsy. IgG anti-beta2-GPI antibodies were associated with the presence of lupus anticoagulant (LA) in addition to the main features of APS. However, antibodies of IgM isotype were related only to thrombocytopenia and heart valve disease. We recommend the evaluation of anti-beta2-GPI antibodies of IgA isotype in addition to IgG in patients with clinical suspicion of APS.
Clin Exp Immunol 1999 Sep
PMID:Isotype distribution and clinical relevance of anti-beta2-glycoprotein I (beta2-GPI) antibodies: importance of IgA isotype. 1046 65


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