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)

Antiphospholipid antibodies (aPL) characterize patients at risk for both arterial and venous thrombotic complications. Recently it has been recognized that the presence of plasma proteins such as beta 2-glycoprotein I(beta 2 GPI) and prothrombin are essential for the binding of aPL to phospholipids and that these proteins are probably the real target of aPL. The discovery of these new antigens for aPL introduces the possibility of new assays to detect the presence of aPL. However, it is not known whether these assays improve the identification of patients at risk for thrombosis. In this retrospective study we compared the value of the classic assays LAC (lupus anticoagulant) and ACA (anticardiolipin antibodies) to detect aPL associated with thrombotic complications, with new assays which are based on the binding of aPL to the plasma proteins prothrombin and beta 2GPI. To do so, we have used these assays in a group of 175 SLE patients and correlated the positivity of the different assays with the presence of a history of venous and arterial thrombosis. Control groups were patients without SLE but with LAC and/or ACA and thrombosis (n = 23), patients with thrombosis without LAC and ACA (n = 40) and 42 healthy controls. In the univariate analysis, in which no distinction has been made between high and low antibody levels, we confirmed LAC and ACA to be related to both arterial and venous thrombosis. Anti-beta 2GPI- and anti-prothrombin-antibodies, both IgG and IgM correlate with venous thrombosis and anti-beta 2GPI-IgM with arterial thrombosis. Multivariate analysis showed that LAC is the strongest risk factor (OR 9.77; 95% CI 1.74-31.15) for arterial thrombosis. None of the other factors is a significant additional risk factor. For venous thrombosis LAC is the strongest risk factor (OR 6.55; 95% CI 2.36-18.17), but ACA-IgM above 20 MPL units also appeared to be a significant (p = 0.0159) risk factor (OR 3.90; 95% CI 1.29-11.80). Furthermore, the presence of anti-beta 2GPI- and/or anti-prothrombin-antibodies in LAC positive patients (n = 60) does not increase the risk for thrombosis. The results showed that (i) the LAC assay correlates best with a history of both arterial and venous thrombosis and (ii) neither the anti-beta 2GPI ELISA nor the anti-prothrombin ELISA gives additional information for a thrombotic risk in SLE patients.
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PMID:Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies. 926 10

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

Lupus anticoagulant (LA) antibodies are acquired inhibitors of coagulation belonging-together with anticardiolipid (aCL) antibodies-to the family of antiphospholipid antibodies. Since LA antibodies affect coagulation reactions via recognition of the complex of lipid-bound prothrombin, they may be better named anti-prothrombin antibodies. We studied their immunological properties in the plasma of 59 patients with antiphospholipid antibodies by means of specific ELISA systems that allowed the characterization of the interaction of these antibodies with human prothrombin and anionic phospholipids. The mode of presentation of prothrombin was found to greatly influence the reactivity of anti-prothrombin antibodies. In fact, when plain polystyrene plates were used to immobilize prothrombin, virtually no binding was observed. Conversely, when prothrombin was coated on high-activated PVC ELISA plates, 34 samples (58%) contained antibodies that recognize human prothrombin in solid phase. In particular, IgG antibodies were found in 21 plasmas and IgM in 22; both IgG and IgM isotypes were present in 9 of these cases. A higher prevalence was observed in the ELISA for the detection of the antibodies directed at the calcium-mediated complex of phosphatidylserine (PS)-bound prothrombin: 53 samples (90%), preadsorbed with cardiolipin liposomes to remove aCL antibodies, showed the presence of IgG and/or IgM anti-prothrombin antibodies. When the results were analyzed according to the immunoglobulin isotypes, 44 (75%) and 39 (66%) samples were found to contain IgG and IgM anti-prothrombin antibodies, respectively. Both IgG and IgM were present in the plasma of 30 patients. Only half of these samples reacted also with PVC-bound prothrombin. Apparently, the higher rate of positivity of the ELISA for the detection of antibodies to the complex of PS-bound prothrombin was not due to differences in the amount of antigen available in the 2 systems, as judged by binding experiments performed with a rabbit polyclonal anti-human prothrombin antiserum. Finally, the anticoagulant properties of 14 total IgG preparations (12 of them contained anti-prothrombin antibodies positive in both ELISA systems, whereas the other 2 cases reacted either with PVC-bound prothrombin only or with PS-bound prothrombin only) were evaluated by diluted Russell's Viper Venom Time and by diluted activated Partial Thromboplastin Time. To rule out the beta 2-glycoprotein I (beta 2-GPI)-dependent anticoagulant effect of the aCL antibodies contained in the preparations, the coagulation tests were performed in beta 2-GPI deficient plasma. Six preparations failed to show anticoagulant activity in both assay systems, suggesting that 2 types of IgG anti-prothrombin antibodies exist, that differ with respect to their anticoagulant properties. These findings suggest that anti-prothrombin antibodies resemble aCL antibodies with respect to the behaviour in "in vitro" coagulation reactions and underline the wide heterogeneity of antiphospholipid antibodies.
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PMID:Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies. 906 99

Antiphospholipid antibodies are a wide family of antibodies, dominated by lupus anticoagulant (LA) and anti-cardiolipin antibodies (aCL), encountered in various circumstances. Unnecessary laboratory tests can be avoided by carefully weighing the indications, especially regarding patient age. Three steps are required to demonstrate LA: screening, mixing studies, then confirmation by neutralization tests. Two coagulation tests at least should be performed aCL are detected with ELISA kits using plates coated with cardiolipin. Due to the large number of kits available and to the lack of agreement on cut-off values, all laboratories must indicate their own standards. Other kits use plates coated with a mixture of phospholipids. Recent data suggest that pathogenic aPL are more specifically directed against phospholipid-associated proteins rather than towards phospholipids. In the future, tests for aCL might be replaced by tests for beta 2-glycoprotein I. The presence of aPL requires a specific treatment only in patients presenting clinical manifestations thought to be aPL-induced (thromboses, fetal losses). Long term warfarin aimed at an INR of 3-3.5 is effective for the secondary prevention of thrombosis. In primary APS, prevention of recurrent miscarriages is frequently achieved by a combination of subcutaneous heparin plus aspirin.
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PMID:[Antiphospholipid antibody/cofactors. What are they? Why, when and how to search for them? Is treatment justified?]. 909 60

The endothelial hybridoma (EAhy926) cell line was employed to clarify whether antiphospholipid antibodies (aPA) [lupus anticoagulant (LA), antiprothrombin antibody (aPT) and/or anticardiolipin antibody (aCL)] and anti-endothelial cell antibodies (AECA) are identical, and establish whether beta2-glycoprotein I (beta2-GPI) is needed for reactivity of aPA to endothelial cells. Ig-G AECA was positive in 9/30 SLE patients with aPA (30.0%) and 10/22 SLE patients negative for aPA (45.5%). Ig-M AECA was positive in one SLE patient with aPA and one SLE patient without aPA. AECA-positivity was not significantly different among unfixed, TNF-stimulated and fixed EAhy926. The influence of beta2-GPI on the reactivity of serum to EAhy926 was minimal, and absorption experiments of serum with cardiolipin-liposome/beta2-GPI or phosphatidylserine-liposome/prothrombin gave little evidence of cross-reactivity of aPA and AECA. The results of our study suggest that aPA and AECA may have partially cross-reacted, but were different antibodies. However, further study is needed to clarify the clinico-pathological significance of AECA.
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PMID:Anti-endothelial cell antibodies to the endothelial hybridoma cell line (EAhy926) in systemic lupus erythematosus patients with antiphospholipid antibodies. 913 70

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

In HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies (aCL) and lupus anticoagulant (LA) has been described. In order to see if these antibodies are isolated or, like in autoimmune diseases, associated with hematological disorders and with antibodies to other phospholipids and to proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1 infected patients, 2. 145 control patients including 61 systemic lupus erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15 patients with stroke, 11 patients with syphilis and 3. 100 blood donors. In HIV-1 infection antiprothrombin (aPrT) antibodies were present in 2% of patients, the prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In contrast with SLE, anti-beta 2-glycoprotein I (4%), LA (1%), biological false positive test for syphilis (0.3%), thrombosis (p < 0.001) were uncommon. In HIV-1 infection, antiphospholipid antibodies do not associated with features linked to them in SLE or syphilis.
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PMID:Autoantibodies to phospholipids and to the coagulation proteins in AIDS. 918 92

The antiphospholipid syndrome is defined as the association between the presence of antiphospholipid antibodies, detected as anticardiolipin antibodies and/or lupus anticoagulant, and a history of either arterial or venous thrombosis and/or recurrent pregnancy loss. Because thrombosis may occur in virtually any organ system, diagnosing the antiphospholipid syndrome and taking appropriate anticoagulation measures are important considerations in all medical specialties. Antiphospholipid antibody-associated thrombosis tends to recur. Antithrombotic prophylaxis to prevent recurrences is therefore needed. Prophylaxis in individuals with circulating antiphospholipid antibodies who have no history of thrombosis is still controversial. Although direct evidence for a pathogenetic role of antiphospholipid antibodies in the development of thrombosis is still lacking, recent studies suggest that it is causative rather than coincidental. New insights on the possible mechanisms leading to thrombosis were provided by the discovery of the serum cofactor (beta2-GPI), a coagulation inhibitor which is required for binding of anticardiolipin antibodies to cardiolipin. More recently, patients with antiphospholipid antibodies were found to possess autoantibodies directed against other coagulation factors, including prothrombin, protein C and protein S. Future studies should clarify whether these different antigenic specificities are associated with particular clinical events and assess the risk of thrombosis associated with the presence of antiphospholipid antibodies in asymptomatic individuals.
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PMID:The clinical significance of antiphospholipid antibodies. 918 33

aPL antibodies are a wide and heterogeneous family of autoantibodies, formerly believed to be directed at anionic phospholipids. In recent years they have been shown to be directed at plasma proteins bound to suitable (phospholipid) anionic surface: beta 2-GPI and prothrombin are the best known and characterized antigens, which are recognized by aCL antibodies and most Lupus Anticoagulants, respectively. The presence of these antibodies has been associated with arterial and venous thrombosis, recurrent miscarriages and thrombocytopenia in the so-called "Antiphospholipid Syndrome". Retrospective and "cross-sectional" studies have established the role of aCL antibodies and Lupus Anticoagulants as risk factors for both venous and arterial thrombosis, the most common clinical manifestations of APS. Prospective studies performed in different patients' populations have validated the association between aCL antibodies and Lupus Anticoagulants with venous and, possibly, arterial thrombosis. Along with the concept of the heterogenity of aPL antibodies there is the observation that among Lupus Anticoagulants aCL-type A, but not LA antibodies, appear to represent a risk factor for thrombosis. However, informations on the predictive value of the various laboratory tests with respect to thrombosis are still rather limited. It is, therefore, necessary to continue the development and standardization of assays that selectively identify aPL antibodies associated with an increased risk of thrombosis, in order to help the clinicians to establish the most appropriate therapeutic strategies for the prevention of the thromboembolic complication of APS.
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PMID:Antiphospholipid antibodies: predictive value of laboratory tests. 919 31

This is a case report of a 34 years old man with Evans syndrome associated with antiphospholipid-protein antibodies. They include lupus anticoagulant and antibodies against cardiolipin, prothrombin and beta 2-glycoprotein I, detected by ELISA. No thrombotic events were observed. The presence of several antibodies directed against surface cell membrane structures in Evans syndrome suggests a common pathogenetic mechanism.
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PMID:[Evan's syndrome with antiphospholipid-protein antibodies]. 927 14


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