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)

It has been reported that antiphospholipid antibodies have the diversity against epitopes and the clinical significance, while the concept of antiphospholipid syndrome has been established. Dr. Harris and Dr. Hughes proposed the diagnostic criteria for antiphospholipid syndrome, and their criteria were widely used. Thrombosis, recurrent fetal loss (intrauterine fetal death), thrombocytopenia, IgG anticardiolipin antibodies and lupus anticoagulants were adopted in their criteria. However, recent studies have revealed the evaluation of the standardization of the methods to detect antiphospholipid antibodies and the clinical significance of both anti-cardiolipin-beta 2-GPI complex antibodies and other isotypes of antiphospholipid antibodies. Thus, the preliminary classification criteria for antiphospholipid syndrome have been discussed. It has been reported that anticoagulation therapy is effective in the management of antiphospholipid syndrome by the recent retrospective studies. It is necessary to confirm these points by the prospective study in the near future.
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PMID:[Diagnosis and management for antiphospholipid syndrome]. 1089 96

The association of antibodies with an apparent specificity for anionic phospholipids with thrombosis, fetal loss, thrombocytopenia, and certain other clinical manifestations is now well-recognized as the antiphospholipid syndrome (APS). Recent advances in our understanding of the antibodies and antigens involved include discovery of the crystal structure of beta2-glycoprotein I, (beta2GPI), genetic studies of beta2GPI polymorphisms, and the development of anti-beta2GPI and antiprothrombin immunoassays as clinical laboratory tests. The identification of antigen-specific T cells in APS patients has stimulated interest in the role of the cellular immune response in the syndrome. Clinical research in APS will also benefit from the development of preliminary classification criteria.
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PMID:Update on antiphospholipid antibodies. 1099 Jan 72

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

The high correlation between the IgG isotype of anticardiolipin antibodies (aCLs) and clinical thrombosis was first documented in 1983, and this observation was confirmed in subsequent studies. In addition, the frequency of fetal loss and thrombocytopenia was increased in this group of patients. These findings were termed the antiphospholipid syndrome (APS). This syndrome was mostly seen in patients with systemic lupus erythematosus (SLE), but it soon became clear that also other patients not suffering from defined SLE might exhibit features of APS. aCL in APS patients are detected in immunoassays by using solid phase cardiolipin as a putative antigen. However, antibodies directed against phospholipid-binding plasma or serum proteins, beta2-glycoprotein I (beta2-GPI), in particular, are also detected. Many recent studies have indicated that one of predominant antibodies that has been identified as aCL in APS patients is against beta2-GPI rather than any of the negatively charged phospholipids. The epitopes recognized by anti-beta2-GPI antibodies raised in APS patients are composed of discontinuous amino acid sequences from the IV domain of human beta2-GPI. These epitopes are cryptic when beta2-GPI does not interact with anionic phospholipids. An early event in atherosclerosis is the accumulation of cholesterol-laden foam cells, which originate mainly from monocyte-macrophage cells by their uptake of chemically modified low-density lipoprotein (LDL). We found that beta2-GPI binds directly to oxLDL, and that the complex of oxLDL and beta2-GPI is subsequently recognized by aCL (anti-beta2-GPI) to be taken up by macrophages. While the pathogenesis of this accelerated atherosclerosis is likely to be multifactorial, it is possible that antiphospholipid antibodies, including aCL (anti-beta2-GPI antibodies), may have contributed to the formation of atherosclerotic lesion.
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PMID:Antiphospholipid antibodies in arterial thrombosis. 1120 78

The primary antiphospholipid antibody syndrome is characterized clinically by the presence of venous and arterial thrombosis, recurrent fetal loss, and thrombocytopenia. The presence of antiphospholipid antibodies is a central serologic finding in primary antiphospholipid antibody syndrome, and plays a critical role in diagnosis. Contrary to initial reports, it is now widely accepted that these autoantibodies are directed predominantly against two antigens: phospholipid-binding plasma protein beta2-glycoprotein I and prothrombin. The mechanism by which antiphospholipid antibodies cause disease is under vigorous investigation. It is hypothesized that antiphospholipid antibodies induce a procoagulant state by binding to antigens on endothelial cells and trophoblast cell surfaces. Indeed, beta2-glycoprotein I appears to function as a cofactor that facilitates this interaction. The resulting endothelial cell activation is associated with cell-surface expression of adhesion molecules that lead to monocyte adhesion - the first steps in thrombosis. Although the precise mechanism that mediates endothelial cell-platelet interaction have not been fully elucidated, platelet binding to the endothelium appears to be the next phase in thrombosis. Thus, the antiphospholipid antibody may be a triggering or activating factor in placental spiral artery thrombosis and subsequent placental infarction. More recently, a role for annexin V has emerged. Studies suggest that thrombosis in the antiphospholipid syndrome may be due to disruption of the annexin shield by antiphospholipid (and cofactor) antibodies, which results in the increased exposure of trophoblasts and endothelial cells to thrombogenic phospholipids.
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PMID:Immunopathogenesis of the antiphospholipid antibody syndrome: an update. 1134 97

In the antiphospholipid syndrome (APS), antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI) are associated with recurrent thromboembolic events, spontaneous abortions, thrombocytopenia and central nervous system (CNS) disturbances. Animals immunized with beta2-GPI develop the systemic manifestations of APS but the involvement of the (CNS) in these animals has not been studied. The objective of the present study was to examine mice with induced experimental APS for behavioral changes. Female Balb/C mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone. Four months after immunization the mice were tested in the staircase apparatus and the following two variables were measured: (1) number of rears: and (2) number of stairs climbed by the mice. Immunization with beta2-GPI resulted in elevated levels of circulating anti-negatively charged phospholipids and anti-beta2-GPI antibodies. The APS mice exhibited hyperactive behavior as reflected by more frequent rears (P < 0.023) and higher number of stairs climbed (P < 0.019) by the mice in 3 min. This simple test demonstrated that experimental APS animals are significantly hyperactive and may serve as a marker for CNS involvement in this model.
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PMID:Hyperactivity in a mouse model of the antiphospholipid syndrome. 1148 Aug 48

Antiphospholipid antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE)) and a hospital-based (87 patients with SLE and 53 with other connective tissue diseases) were investigated for APA and associated clinical manifestations. Anticardiolipin antibodies (ACA) of IgG and IgM classes were found in 13 and 38% of the population-based patients and in 29 and 58% of the hospital-based patients, respectively. The corresponding figures for antibodies against beta2-glycoprotein I (anti-beta2GPI) were 15 and 10% in the population-based patients and 14 and 8% in the hospital-based cohort. Anti-beta2GPI antibodies were always found in association with the corresponding immunoglobulin class of ACA. In both cohorts anti-beta2GPI of the IgG class were associated with arterial/venous occlusion, a result concordant with other studies. A novel finding in both cohorts, however, was an association between thrombocytopenia and IgM anti-beta2GPI.
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PMID:Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia. 1153 Sep 94

The antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis, recurrent pregnancy loss, and thrombocytopenia combined with laboratory tests that indicate the presence of antibodies against phospholipid-binding proteins. The antibodies are directed against a complex of phospholipid with a protein such as beta 2-glycoprotein I (beta 2-GPI) or prothrombin and are detected by means of phospholipid-dependent coagulation assays (known as assays for lupus anticoagulants) and by ELISAs that contain beta 2-GPI and a phospholipid (e.g., cardiolipin). The antiphospholipid syndrome can be associated with other connective tissue disorders such as systemic lupus erythematosus or may be the only manifestation of an autoimmune disorder. Management of patients with this disorder usually includes anticoagulation, which has been found to reduce the rate of recurrence of venous and arterial thrombosis as well as the rate of fetal loss.
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PMID:Diagnosis and management of patients with the antiphospholipid syndrome. 1171 94

The antiphospholipid syndrome (APS) is a disorder of hypercoagulability, characterised by thromboembolic events, repeated miscarriages and thrombocytopenia in association with circulating antiphospholipid antibodies. These antibodies are directed against epitopes on either oxidised phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or against the glycoprotein itself. Renal manifestations of the APS are varied and depend on the type of renal pathology present. The renal vasculature may be affected by either a small vessel, thrombotic microangiopathy process or by large vessel thrombosis. In patients with end stage renal disease, the prevalence of antiphospholipid antibodies may increase with time on dialysis. Anticardiolipin antibodies have been associated with a high incidence of haemodialysis access clotting, a major source of morbidity and hospitalisation in end stage renal disease patients. In renal transplant recipients, antiphospholipid antibodies may be associated with a higher incidence of primary graft non-function, particularly in patients without a history of pretransplantation haemodialysis. Complications of the APS during pregnancy span all trimesters and include intrauterine growth retardation, placental abruption, pre-eclampsia, preterm labour and recurrent fetal loss. As these women have a high risk of recurrent fetal loss, multiple treatment modalities have been investigated, including aspirin, heparin, prednisone and intravenous immunoglobulin. Various treatment strategies for the APS have been developed and are based on a combination of anticoagulant therapy with either warfarin or heparin, along with antiplatelet therapy with aspirin. Experimental treatments involving immunomodulatory therapy with intravenous immunoglobulin, apheresis and novel antibody therapy are being investigated with hopes of successful clinical applications.
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PMID:Nephrological and obstetric complications of the antiphospholipid syndrome. 1203 25

We describe a patient with antiphospholipid antibody syndrome (APS) who died because of relentless inferior vena cava (IVC) tumor thrombosis due to an unsuspected leiomyosarcoma. Laboratory confirmation for APS was provided by functional identification of a lupus anticoagulant and anticardiolipin IgG and anti-beta2-glycoprotein I IgM antibodies. Although sensitive for detecting vascular obstruction, radiocontrast venography and magnetic resonance imaging and angiography detected the IVC thrombosis but failed to distinguish its malignant nature. Concomitant refractory thrombocytopenia prevented further invasive diagnostic and therapeutic maneuvers for progressive, severe IVC thrombosis unresponsive to aggressive treatment of APS. Deep venous thrombosis refractory to anticoagulant and immunomodulatory therapies in a patient with APS may be due to a concomitant underlying malignancy, such as a leiomyosarcoma, causing vascular obstruction.
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PMID:Fatal tumor thrombosis due to an inferior vena cava leiomyosarcoma in a patient with antiphospholipid antibody syndrome. 1205 32


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