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)

Recent evidence suggests that lupus anticoagulants are immunologically distinct from the anticardiolipin antibodies. Nevertheless, the associated clinical complications exhibited by the two groups of antibodies are similar. They have been shown to have a strong association with a history of arterial and venous thrombosis, thrombocytopenia and neurological disease in patients with SLE or lupus-like disorders. The association between antiphospholipid antibodies and recurrent fetal loss is suggested by the currently available data but is not firmly established. Patients with lupus and antiphospholipid antibodies and an established history of recurrent fetal wastage are at high risk for experiencing subsequent fetal loss, but it is not yet known whether the same is true for patients without a history of fetal loss. The association of thrombosis, neurological disease, thrombocytopenia, and fetal loss in patients with non-SLE disorders has not been as extensively studied. Only recently have investigators such as Ginsberg and colleagues begun to show in prospective studies that there may, in fact, be a statistically significant risk of thrombotic events in otherwise healthy individuals with antiphospholipid antibodies. Many of the diverse minor manifestations reported in individual patients, case series, or cross-sectional studies such as livedo reticularis, leg ulcers, and hemolytic anemia may, alternatively, be due to coincidence or chance. Efforts to elucidate the mechanisms of thrombosis in patients with antiphospholipid antibodies is an area of active research. Most efforts have been based on the effects of these antibodies on endothelial cell and platelet function as well as on the fibrinolytic system. In addition, it has recently been shown that binding of antiphospholipid antibodies to phospholipids requires the serum "co-factor" beta 2-glycoprotein I. In patients with SLE selected for the presence of the lupus anticoagulant, thrombosis, or fetal loss, Viard and associates found that 17 of 47 (36%) patients had anti-beta 2-glycoprotein I antibodies. They were able to show, in their small retrospective study, that there was an association between the presence of these antibodies and anticardiolipin activity, lupus anticoagulant activity, and thrombotic events, but not with spontaneous abortion. Of patients with SLE and thrombosis (9 of 47) eight of nine were positive for anti-beta 2-glycoprotein I antibodies, seven of nine were positive for anticardiolipin antibodies, and eight of nine were positive for the lupus anticoagulant. The known inhibitory effect of beta 2-glycoprotein I on platelet aggregation, on platelet prothrombinase activity, and on the intrinsic pathway of coagulation supports the hypothesis that implicates beta 2-glycoprotein I in the pathogenesis of unwanted thrombotic events.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical syndromes associated with lupus anticoagulants. 805 30

The antiphospholipid syndrome (APS) is defined as the association of antiphospholipid antibodies (aPL) with arterial or venous thrombosis, recurrent fetal loss, thrombocytopenia or neurologic disorders. Some aPL can be detected via phospholipid dependent coagulation assays where they present as an aspecific coagulation inhibitor termed the lupus anticoagulant (LA). Other antibodies can be measured via immunological assays mostly via their capability to bind to immobilised cardiolipin and are therefore called anticardiolipin antibodies (aCL). Affinity purification of aCL led to the discovery that, in contrast to what the term antiphospholipid antibody could suggest, these autoimmune antibodies do not bind to negatively charged phospholipids per se but to beta-2-glycoprotein I (beta 2GPI), a phospholipid-binding protein eventually bound to phospholipid surfaces. LAs have been found to be directed towards either prothrombin or beta 2GPI bound to anionic phospholipids. Whereas clinical and animal experimental data clearly suggest a role for beta 2GPI-dependent aPL in the development of the APS, the pathogenic mechanism is not known. Interferences with several phospholipid dependent anticoagulant pathways have been proposed but none of these has received general acceptance. Based on clinical and experimental similarities with heparin-induced thrombocytopenia, another syndrome of antibody mediated thrombosis, we proposed a model of prothrombotic cellular activation. This model, although supported by a number of experimental observations, does not provide a direct explanation for the recent observation that LA are more strongly associated with thrombosis than aCL. In order to study this, we raised murine monoclonal antibodies (moab) against human beta 2GPI. These antibodies, of which some had LA activities and others not, enabled us to study the interaction between beta 2GPI, antibody and phospholipids. In contrast to what was generally accepted, beta 2GPI appeared to have only low affinity for coagulation promoting phospholipids. In the presence of LA positive anti-beta 2GPI moabs, the affinity of beta 2GPI for phospholipids increased significantly. This appeared to be dependent on the formation of bivalent beta 2GPI-antibody complexes on the phospholipid surface. It is conceivable that such bivalent complexes also remain tightly attached to membranes of activated cells enabling further thrombosis promoting activation via Fc receptor interaction or the complement system, a hypothesis that is currently being investigated. Further studies also showed that our LA positive anti-beta 2GPI moabs have a potential for the production of LA control specimens, that could be made available to routine hemostasis laboratories to assess intra-laboratory precision of LA testing, to manufacturers to produce highly sensitive assay systems and to control batch-to-batch variability of their reagents and to organizations involved in external quality assessment. In conclusion this work has enabled us to understand the molecular mechanism by which certain autoimmune antibodies found in patients with APS prolong coagulation assays in vitro. The antibodies generated are an important tool to improve the laboratory diagnosis of the lupus anticoagulant and may help us clarify the pathogenic role of autoimmune anti-beta 2GPI antibodies.
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PMID:The role of beta 2-glycoprotein I-dependent lupus anticoagulants in the pathogenesis of the antiphospholipid syndrome. 1114 85

High-sensitive C-reactive protein (hs-CRP) is a marker of inflammation which has been shown in several prospective studies to independently predict myocardial infarction, stroke and peripheral artery disease. Patients with antiphospholipid antibodies (aPL) are at increased risk of recurrent thromboembolic events, but the possibility of predicting this risk seems rather limited. Similarities were recently found between aPL and CRP in the pathology of thrombosis. The current study investigated the predictive role of hs-CRP in a cohort of patients with neurological manifestations. A follow-up investigation was done in a cohort of 55 aPL-positive patients with acute manifestations of neurological disease. hs-CRP levels were measured in all patients at enrollment and were compared to the patients' condition after a median period of 32 months. Lupus anticoagulants were detected according to the Standardization of Lupus Anticoagulants (SSC) of the ISTH. Anticardiolipin tests were performed by a beta2-glycoprotein I-dependent enzyme-linked immunsorbent assay (Pharmacia ELISA). hs-CRP was measured by latex-enhanced turbidometry (dimension RXL, Dade Behring). Cerebral infarctions and transient ischemic attacks were the most frequent cerebral events. In patients with aPL, elevated levels of hs-CRP were closely associated with an increased rate of recurrent or residual symptoms (OR, 12.5; 95% CI, 3.72-41.94) and were not related to other risk factors, except smoking (p<0.05). The rate at which a given patient's condition deteriorated was also related to the level of hs-CRP. In patients with antiphospholipid syndrome (APS), elevated levels of hs-CRP may identify a group of patients which is at high risk of recurrent or residual neurological symptoms and which may benefit from more careful follow-up and from antithrombotic therapy.
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PMID:Predictive role of hs-C-reactive protein in patients with antiphospholipid syndrome. 1632 94

Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired thrombophilia. It is characterized by the presence of antiphospholipid antibodies (APL) that are directed against phospholipid-binding plasma proteins, such as beta-2-glycoprotein I (b2GPI). Its main manifestations are recurrent vascular thromboses (so-called "thrombotic APS") and pregnancy complications ("obstetric APS"). According to the current consensus criteria, a persistently positive functional lupus anticoagulant (LA) assay and/or the presence of anti-b2GPI and/or anti-cardiolipin antibodies, together with clinical symptoms, is mandatory for the diagnosis of APS. Other clinical features, such as thrombocytopenia, Coombs-positive haemolytic anaemia, heart valve disease, renal microangiopathy and neurologic disorders are also common in APL-positive patients. APS can be associated with other autoimmune disorders, such as systemic lupus erythematosus. In rare cases, catastrophic APS (CAPS) occurs, with the development of excessive thrombosis at multiple sites, usually affecting small vessels and leading to multi-organ dysfunction and organ failure. Treatment usually comprises antithrombotic therapy using antiplatelet and anticoagulant agents. However, there is no consensus concerning the intensity or duration of therapy. Despite apparently adequate anticoagulation, the risk of recurrent thrombosis remains high. For patients with CAPS, a combined therapeutic approach that includes anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulin seems to be the best treatment option. Keywords: Antiphospholipid syndrome, lupus anticoagulants, anti-cardiolipin, anti-beta-2-glycoprotein I, vascular thrombosis, pregnancy complication.
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PMID:Antiphospholipid syndrome - an update. 3020 64