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 (aPL) antibodies include anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies. LA antibodies recognize the complex of lipid-bound (human) prothrombin, in this way inhibiting the phospholipid-dependent coagulation reactions, whereas aCL antibodies are directed towards beta 2-glycoprotein I (beta 2-GPI) bound to an anionic lipid surface. According to their behavior in coagulation reactions, we have divided aCL antibodies into two groups: aCL-type A, which inhibit the phospholipid-dependent coagulation reactions because they enhance the binding of beta 2-GPI to the procoagulant phospholipid surface; and aCL-type B antibodies, which are devoid of anticoagulant properties. We report the distinctive laboratory and clinical profiles of 25 patients with well-characterized, phospholipid-dependent inhibitor of coagulation. Fourteen patients had LA antibodies (aCL-type B were concomitantly present in 10 cases, while in the other four, aCL titer was normal), and the other 11 had aCL-type A antibodies. The laboratory evaluation of the two groups showed the dilute Russell viper venom time (dRVVT) to be the most abnormal coagulation test in the aCL-type A-positive group, whereas the kaolin clotting time (KCT) was the most abnormal assay in the LA-positive group. In fact, the ratios of the coagulation times of patient plasma over normal pooled plasma (mean +/- standard deviation) for LA versus aCL-type A antibodies were 1.48 +/- 0.27 versus 2.20 +/- 0.42, P = .0001, and 2.22 +/- 0.42 versus 1.50 +/- 0.42, P = .0003, for the dRVVT and KCT, respectively. No differences were observed either in the ratios of the activated partial thromboplastin times and the prothrombin times or the plasma levels of beta 2-GPI and prothrombin. Conversely, aCL titers were significantly higher in aCL-type A-positive patients (147 +/- 44 U) than in the LA-positive group (61 +/- 55 U; P = .0003). We ruled out the possibility that platelet contamination of plasma could account for the observed coagulation profiles, as the two patterns were reproduced in platelet-free plasma. In addition, we performed clotting tests in plasma in the presence of phospholipids and calcium after addition of factor IXa or factor Xa. The assay performed with factor Xa was more sensitive to the presence of aCL-type A antibodies, while the assay performed with factor IXa was preferentially sensitive to LA-containing plasmas, supporting the earlier findings with the dRVVT and KCT assays.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kaolin clotting time and dilute Russell's viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein I-dependent antiphospholipid antibodies. 760 91

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.
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PMID:Antiphospholipid antibody: future developments. 780 22

There has been a recent, dramatic surge in interest in antiphospholipid antibodies and associated clinical disorders, especially focal ischemic cerebrovascular disease. Antiphospholipid antibodies are a heterogeneous group of antibodies with varying specificities. Coagulation assays will detect lupus anticoagulants while enzyme-linked immunosorbent assays detect anticardiolipin antibodies. There are numerous potential links between antiphospholipid antibodies and coagulation disorders, including interaction of antiphospholipid antibodies and a cofactor, beta 2-glycoprotein I, which itself is involved in coagulation mechanisms. While the specific mechanism of antiphospholipid antibody-related coagulopathy is unknown, it is clear that antiphospholipid antibodies are associated with an immune-mediated prothrombotic state. Patients with the highest titers of IgG antiphospholipid antibodies have a relatively high risk of recurrent thrombotic events, especially stroke, deep venous thrombosis, and spontaneous abortion. Because of limited controlled, prospective data, current therapy remains empiric and directed at coagulation mechanisms, immune mechanisms, or both.
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PMID:Cerebrovascular disease with antiphospholipid antibodies: immune mechanisms, significance, and therapeutic options. 896 22

The term "antiphospholipids" (aPLs) refers to an heterogeneous family of antibodies diagnosed either by clotting tests: the lupus anticoagulants or by Elisa: anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2GP1) especially. aPLS recognize phospholipids, alone or bound to plasma protein cofactor(s), or the cofactors themselves. aPLs have long been described in autoimmune diseases such as SLE, but may also be found in other clinical settings including infections, malignancies and drug administration. Their persistent presence can be associated with venous and/or arterial thrombotic complications and/or recurrent miscarriage, thus defining the "antiphospholipid syndrome" (APS). The heterogeneity of aPLs makes a comprehensive approach to laboratory investigation essential. Detection of lupus anticoagulants relies on increased clotting times in phospholipid-dependent tests. Their 4 step diagnosis includes: 1) screening (by at least two different tests); 2) demonstration of an inhibitory activity; 3) evidence of its phospholipid dependence; 4) exclusion of an associated coagulopathy. Among the aPLs detected by Elisa, IgG aCL are the most frequently investigated. However, other antibodies may represent useful biological tools. Among them, anti-beta2GP1 are thought to be more closely associated with a history of thrombosis than aCL and testing for anti-beta2 GP1 should now be systematically included in the biological diagnosis of APS. The Elisa used for aCL and anti-beta2GP1 are not fully standardized, and a number of methodological parameters may account for the interlaboratory discrepancies often observed. The clinical importance of other antibodies such as antiphosphatidylethanolamine, antiprothrombin or antiannexin V is being evaluated. An appropriate laboratory investigation of APS should, in all cases, combine the use of clotting and immunological assays, and assess the persistence of autoantibodies over time.
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PMID:[Antiphospholipid antibodies: clinical significance and biological diagnosis]. 1102 99