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 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.
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PMID:Antiphospholipid antibodies and atherosclerosis. 890 78

Lupus anti-DNA may have higher homology with germline than those from normal subjects. However, in NZB/NZW mice, bacterial DNA is more antigenic than mammal DNA, which could indicate an antigen-driven origin. High-affinity antibodies to double-stranded DNA cross-react with small nuclear ribonucleoprotein and ribosomal P proteins. These cross-reactive anti-DNA may penetrate live cells. Antibodies to ribosomal P proteins are associated with neuropsychiatric, renal, and hepatic lupus involvement. IgG antibodies to (H2A-H2B)-DNA complexes antedate procainamide-induced lupus. Autoantibodies to some La/Ro peptides in a mother indicates that her children may develop neonatal lupus and determine who will have congenital heart block. Perinuclear antineutrophil cytoplasmic antibodies are present in 25% of systemic lupus erythematosus patients without correlation with anti-DNA or disease activity. Different antiphospholipid antibodies require different protein cofactors for reactivity. Those to anionic phospholipids require beta 2-glycoprotein I, whereas anti-phosphatidylethanolamine antibodies require kininogen or its binding protein. Antibodies to phospholipid-free beta 2-glycoprotein I are associated more strongly with clinical antiphospholipid syndrome than are antiphospholipid antibodies.
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PMID:Autoantibodies in systemic lupus erythematosus. 894 42

Antiphospholipid antibodies are a heterogeneous group of autoantibodies with clinical importance because of their strong association with thrombotic events. Recent evidence have shown that antiphospholipid antibodies are not directed against phospholipids, as has previously been thought, but are a part of a large family of autoantibodies against phospholipid-binding plasma proteins. So far, one of the most common and best characterized antigenic target is beta 2-glycoprotein I (beta 2-GPI), which plays an important role in the binding of anticardiolipin antibodies (aCLA) to cardiolipin. The detection of anti-beta 2-GPI antibodies by using a simple and rapid ELISA may facilitate the recognition of alpha "pathogenic" alpha aCL in antiphospholipid syndrome.
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PMID:Clinical significance of anti-beta 2-glycoprotein I antibodies. 895 53

Phospholipid dependent antibodies are usually measured with assays for antiphospholipid/anticardiolipin antibodies (aPLA) or for lupus anticoagulant (LA) activity. Most of them are targeted to complexes of beta 2-glycoprotein I (beta 2-GPI) and anionic phospholipids (PLP) or to prothrombin for some LA. New understandings allow a better standardisation and optimisation of assays' reactivity. Antigenic targets of phospholipid dependent antibodies were studied on plasmas from 38 patients with the antiphospholipid syndrome (APS) and presenting aPLA and/or LA. Using human beta 2-GPI-PLP complexes as solid phase antigen offers the highest sensitivity for measuring aPLA. Many aPLA, but not all, also react with beta 2-GPI coated on solid phase, however there is no evidence until now that this latter reactivity shows a closest association with the clinical context. Most of the patients with LA present an immunological reactivity to beta 2-GPI alone or to prothrombin, when these proteins are coated on solid phase. In two cases there was a reactivity to only beta 2-GPI-PLP complexes. For the various immunoassays, using NUNC type I plates offers a good binding capacity for coating antigens. They are then present at enough density on solid phase for insuring an efficient binding of autoantibodies. This is an important factor for assay sensitivity and reproducibility. Interestingly, in 1 case with LA, autoantibodies were reactive with coated beta 2-GPI alone but not with its PLP-complexes. In another case reactivity to beta 2-GPI was much higher than that to beta 2-GPI-PLP.
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PMID:Different target specificities of phospholipid-dependent antibodies. 895 54

The clinical significance of anti-beta 2 glycoprotein I (beta 2-GPI) antibodies was evaluated in patients with antiphospholipid syndrome (APS), primary and secondary to systemic lupus erythematosus (SLE). Anti-beta 2-GPI were tested in 120 patients (39 primary APS, 32 APS with SLE and 49 SLE without APS) by ELISA utilizing irradiated plates in the absence of cardiolipin. Anticardiolipin antibodies (aCL) and antiphosphatidylserine antibodies were also measured in the same patients using standardized assays. Anti-beta 2-GPI titres correlated strongly to those of aCL (r = 0.816, P = 0.0001), and to those of antiphosphatidylserine antibodies (r = 0.841, P = 0.0001). Anti-beta 2-GPI were detected in 53.5% of APS patients (38/71), but only in 4.1% of SLE patients without APS (2/49). In the latter group, 24.5% (12/49) of patients had a positive titre of aCL. The anti-beta 2-GPI assay showed higher specificity for APS than the aCL in APS (96 vs 75%, respectively, chi 2 = 6.75, P = 0.00094). Our findings suggest that the assay of anti-beta 2-GPI may improve the specificity for APS.
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PMID:Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome. 940 76

Lupus anticoagulant (LA) is a general term to define immunoglobulins interfering with phospholipid-dependent coagulation tests. It is now clear that the phospholipid-dependence of some LA is related to the presence of the phospholipid-binding plasma protein beta 2-glycoprotein I (beta 2-GPI) and that autoantibodies to beta 2-GPI might represent a specific category of LA. To verify this hypothesis we have purified IgG autoantibodies to beta 2-GPI from plasma of 6 patients with antiphospholipid antibody syndrome, by means of agarose-immobilized human beta 2-GPI. All 6 preparations tested positive in anti-beta 2-GPI IgG antibody ELISA and showed a marked LA activity by prolonging dilute Russell Viper Venom Time (dRVVT) from a minimum of 5.3 s in patient # 1 to a maximum of 41.1 s in patient # 3. These IgG preparations behaved as typical LA, with this activity tending to disappear in the presence of increasing phospholipid (PL) concentrations. Moreover, the LA activity of the IgG preparations was not detectable in the absence of PL, in which case the ratio between dRVVT obtained in the presence and absence of IgG autoantibodies to beta 2-GPI was close to 1. This pattern was confirmed by using plasma from patients with antiphospholipid antibody syndrome testing positive for anti-beta 2-GPI IgG antibodies. These findings suggest that dRVVT performed both in the presence and absence of PL might constitute a sensitive screening test to detect specific antibodies with LA activity.
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PMID:Utilization of dilute Russell's viper venom time to detect autoantibodies against beta 2-glycoprotein I which express anticoagulant activity in the presence but not in the absence of exogenous phospholipids. 903 61

Anticardiolipin antibodies (aCL) in the sera of patients with antiphospholipid syndrome (APS) recognize an altered structure of beta 2-glycoprotein I (beta 2-GPI) interacting with solid-phase negatively charged phospholipids. beta 2-GPI bound to Cu2+-oxidized plasma lipoproteins, i.e. oxidized very low-density lipoprotein (oxVLDL), oxidized low-density lipoprotein (oxLDL), or oxidized high-density lipoprotein (oxHDL). beta 2-GPI inhibited in vitro uptake, i.e. cell surface binding, cellular association, and proteolytic degradation of oxLDL by murine macrophage J774A.1 cells. The binding of oxLDL to the macrophages was inhibited by the addition of polyinosinic acid (poly (I)), a competitor of the scavenger receptor, but not by another polyanionic acid, polycytidylic acid (poly (C)). Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human beta 2-GPI and monoclonal aCL derived from NZW x BXSB F1 (WB F1) mice, an animal model of APS, or anti-beta 2-GPI antibodies from BALB/c mice immunized with human beta 2-GPI. These findings indicate that beta 2-GPI may be an antiatherogenic protein and that the autoimmune response against beta 2-GPI may have a role in the development of atherosclerosis in APS.
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PMID:Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. 906 34

We studied anti-beta 2-glycoprotein I antibodies (a beta 2GPI) in autoimmune disease patients to evaluate their relationship to clinical findings. Seventy-nine systemic lupus erythematosus (SLE) patients [44 with antiphospholipid antibodies (aPL)], 21 with primary antiphospholipid syndrome (APS), eight asymptomatic individuals with aPL and 60 controls were studied. Sixteen SLE patients (14 with aPL and two without aPL) and six with primary APS had a beta 2GPI. A significant relationship was found between a beta 2GPI and aPL (P < 0.01). In SLE, a significant correlation was found between previous thrombosis or thrombocytopenia and a beta 2GPI or a beta 2GPI + aPL, but not between fetal losses and a beta 2GPI. These data suggest that a beta 2GPI may be useful in the study of APS.
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PMID:Anti-beta 2-glycoprotein I antibodies: a useful marker for the antiphospholipid syndrome. 911 49

A 33-year-old man presented malar rash in April, 1992. The rash had gradually developed and he was admitted to our hospital in February, 1994. Laboratory findings showed proteinuria of 0.5-0.8 g/ day, thrombocytopenia (4.8 x 10(4)/mm3), false positive serologic test for syphilis, anti-nuclear antibody with a speckled type at a titer of 1 : 80. Activated partial thromboplastin time was prolonged (41.3 s), and anti-beta 2-GPI antibody was strongly positive (56.6 U/ml on enzyme linked immunosorbent assay). The diagnosis of systemic lupus erythematosus with antiphospholipid syndrome was made and prednisolone 60 mg/day improved his manifestations. He could be discharged in July, 1994. Nine months after the discharge he developed dyspnea, and he was admitted to our hospital again. On admission the blood pressure was 212/170 mmHg, Levine III/VI systolic murmur was noted at the apex of heart. Significant laboratory findings showed as follows: WBC 15, 110/mm3 (Neu 73%, Lym 18%), RBC 380 x 10(4)/mm3, Hb 10.2 g/dl, Plt 20.0 x 10(4)/mm3, GOT 23 IU/l, GPT 21.
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PMID:[Acute cardiac failure due to dilated cardiomyopathy in systemic lupus erythematosus with antiphospholipid antibody]. 912 25

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


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