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 autoantibodies particularly antibodies against beta2-glycoprotein I (anti-beta2GPI) are casually associated with thromboses in patients with autoimmune diseases. However, their exact prevalence and role in the pathogenesis of thromboses in the absence of autoimmune disease is still inconclusive. They might be particularly important when other risk factors of thrombosis are absent. We investigated antiphospholipid antibodies in 68 young women (aged <45yr at onset of the event, without autoimmune disease and with an otherwise low risk of thrombosis) in the stable period following myocardial infarction (MI), lacunar cerebral infarction (LACI) or deep vein thrombosis (DVT) and in 37 healthy age-matched controls. Patients had increased IgM anti-beta2GPI compared to controls (36.0, 11.5-49.5 vs. 17.50, 3.50-30.0 arbitrary units (AU), p<0.001), whereas no difference was obtained in other measured antibodies (anticardiolipin and antiphosphatidylserine (aPS) antibodies of IgG and IgM). IgM anti-beta2GPI positively correlated with some markers of increased coagulation potential and negatively with BMI (r=-039, p<0.005) and other parameters of the metabolic syndrome. In conclusion, we found that levels of IgM anti-beta2GPI are increased in young women suffering arterial or venous thromboses in the absence of other known autoimmune diseases and also in the absence of pronounced classical risk factors. We found that IgM anti-beta2GPI positively correlated with some markers of increased coagulation potential and negatively with parameters of the metabolic syndrome. Thus, it appears that elevated levels of IgM anti-beta2GPI are linked to thrombotic disorders in young women (without autoimmune disease) particularly when classical risk factors or the metabolic syndrome are absent.
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PMID:Anti-beta 2-glycoprotein I antibodies of IgM class are linked to thrombotic disorders in young women without autoimmune disease. 1741 86

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with the persistence of lupus anticoagulant or anticardiolipin (aCL) antibodies. Accumulating evidence indicates that phospholipid binding protein, beta2-glycoprotein I (beta2GPI) represents the major target antigen for antiphospholipid (aPL) antibodies and plays a role in the pathogenesis of APS. It is widely accepted that aPL antibodies detected by conventional solid phase assays in patients with APS are mainly directed against a complex of aCL and anti-beta2GPI, although antibodies against beta2GPI protein can now also be detected by specific ELISA using purified proteins in solid phase. Despite the fact that these antibodies are not listed in the new diagnostic criteria, a high specificity of anti-beta2GPI assay for the clinical features of APS was established. During the last decade, numerous studies have investigated the clinical link between aCL and/or anti-beta2GPI antibodies and diverse features of APS. This manuscript reviews the current studies published recently in this field and discusses the relationship between the existence of aCL and anti-beta2GPI antibodies and the main and unusual manifestations of APS.
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PMID:Novel insights into associations of antibodies against cardiolipin and beta2-glycoprotein I with clinical features of antiphospholipid syndrome. 1791 84

Atherosclerosis (AT) is a metabolic, systemic inflammatory/immune disease characterized by lipoproteins metabolism alteration that leads to immune/inflammatory system activation with the consequent proliferation of smooth-muscle cells, narrowing arteries and atheroma formation. Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombophilic state and circulating antiphospholipid antibodies (aPL) including anti beta2-GPI. Experimental studies and human observations suggest that APS is associated with AT. In fact, innate and adaptive immune responses participate in the pathogenesis of both diseases. Anti-oxLDL, anti-aPL, anti beta2GPI, anti-HSP antibodies, among others, has been found in patients with APS and AT. Endothelial dysfunctions, oxidative stress, increase of cell adhesion molecules, active platelets, are common findings in both diseases. Macrophages, dendritic cells, T-cell activation, CD40-CD40 ligand interaction, are considered as pathogenic mechanism of AT and APS. Premature AT may be the first symptom of APS. Thrombophilia, aPL antibodies, and APS may be present in patients with premature AT. An association between AT and venous thrombosis (a clinical hallmark of APS) has been proposed in unselected patients with deep venous thrombosis of the legs without symptomatic AT. Asymptomatic AT, defined in terms of carotid intima media thickness and lumen diameter decrease, was observed in patients with APS. Premenopausal female patients with PAPS have a higher prevalence of cerebrovascular disease in comparison with male patients. Accelerated AT and hormones could be the explanation of these findings. High levels of aCLs, significantly predict the risk of future ischemic stroke in women but not in men. AT is one of the main features of systemic APS and offer opportunities for new treatment strategies.
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PMID:Systemic antiphospholipid syndrome and atherosclerosis. 1791 89

The diagnosis of the antiphospholipid syndrome, a non-inflammatory autoimmune disease characterized by thrombosis or pregnancy morbidity in the presence of antiphospholipid antibodies, depends greatly upon laboratory diagnostics. The diagnostic value of all available assays to detect antiphospholipid antibodies and the anticardiolipin assay in particular, is a matter of ongoing debate. Although the presence of lupus anticoagulant correlates best with thrombosis, accurate determination is not always possible due to anticoagulant treatment. Data on the predictive value of alternatives such as the anti-beta2-glycoprotein I and the anti-prothrombin antibody assay are insufficient and prospective cohort studies are needed. Determining antiphospholipid antibody profiles seems to increase diagnostic specificity. Substantial progress has been made in unravelling the pathophysiological mechanisms underlying the antiphospholipid syndrome. Several cellular receptors for antibody-beta2-glycoprotein I complexes have been identified and their roles in cellular activation are being investigated. In vivo data should provide more insight into the importance of the interaction with individual receptors.
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PMID:Current insight into diagnostics and pathophysiology of the antiphospolipid syndrome. 1796 17

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The sCD21 is able to bind all known ligands such as CD23, sCD23, Epstein-Barr virus and C3d in immune complexes. Here, we show the serum levels of sCD21 in sera the of antiphospholipid syndrome (APS) patients. Antiphospholipid syndrome is an autoimmune disorder in which autoantibodies cause heart attack, stroke and miscarriage. Antiphospholipid syndrome may appear as primary or in association with systemic lupus erythromatosus (SLE) and other autoimmune diseases. Here, we ask whether APS patients have different sCD21 titers compared to healthy persons and whether sCD21 levels correlate with the presence of anti-beta2-GPI autoantibodies. We show that autoimmune APS patients have significantly reduced amounts of sCD21 in their sera, irrespective of the presence of anti-beta2-GPI autoantibodies. In our APS patients cohort additional SLE, vasculities, DVT (deep vein thrombosis), fetal loss or thrombosis did not correlate to the reduced level of sCD21.
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PMID:Antiphospholipid syndrome patients display reduced titers of soluble CD21 in their sera irrespective of circulating anti-beta2-glycoprotein-I autoantibodies. 1817 55

Antiphospholipid syndrome is an autoimmune disorder in which the body produces antibodies to its own phospholipids or plasma proteins. Antiphospholipid syndrome (APS) is associated with many pathologies with several clinical manifestations. It can occur as a primary disorder or may be secondary to connective tissue disorder or tumor. Anti-phospholipid antibodies were detected in two categories of patients: in one group with many clinical manifestations (such as thrombotic events, thrombocytopenia and miscarriages) and in the other group with few clinical manifestations. In the first group high levels of IgG and IgA antibodies resulted, in the other group low levels of IgM. The ratio male:female was 1:3.5. Out of the 700 patients examined, 12 resulted positive for anti-cardiolipin (aCL) and a-beta2-GPI (affected by APS), and 15 patients positive for aCL (with middle-high values) but negative for a-beta2-GPI. At this point, according to the guidelines, we could have stopped examining. Only by continuing diagnostic investigation for these 15 patients has it been possible to observe: 2 patients positive for anti-thrombin (important first marker in the diagnosis of venose and arterial thromboses), anti-phosphatidylserine and anti-phosphatidylinositol (markers for cerebral diseases and recurrent miscarriages); 1 patient positive for anti- phosphatidylserine; 1 patient positive for anti-phosphatidylinositol antibody; 1 patient positive for both anti-phosphatidylserine and anti-phosphatidylinositol; 10 patients positive only for anti-cardiolipin. According to the results obtained, and considering that a more accurate investigation permitted to better identify APS syndrome, we propose a new diagnostic procedure.
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PMID:A new diagnostic approach to better identify antiphospholipid syndrome. 1854 83

The objective of our study was to evaluate the significance of extended antiphospholipid profile in patients with venous thromboembolism without any systemic autoimmune disease. In 140 patients (age 18-69 years; 47.1% men) with venous thromboembolism and 136 control participants we tested anticardiolipin antibodies, anti-beta 2 glycoprotein I (anti-beta2-GPI) and also non-criteria antiphospholipid antibodies: antiphosphatidic acid, antiphosphatidylethanolamine, antiphosphatidylglycerol, antiphosphatidylinositol, antiphosphatidylserine. Commercial and in-house enzyme-linked immunosorbent assays were used. The antibodies with significantly higher prevalence in patients (compared to controls) were: immunoglobulin (Ig) M-anticardiolipin antibodies (12.9%; P = 0.035), IgG-anti-beta2-GPI (16.4%; P = 0.0032), IgM-antiphosphatidylethanolamine (14.3%; P = 0.014). In most cases, these three antibodies did not overlap. In conclusion, of non-criteria antiphospholipid antibodies, only antiphosphatidylethanolamine were significantly more prevalent in patients with venous thromboembolism, with only minor overlapping with the criteria antiphospholipid antibodies. Our results suggest the possible utility of searching for antiphosphatidylethanolamine in the clinical suspicion of antiphospholipid syndrome and the absence of criteria antiphospholipid antibodies.
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PMID:Laboratory evaluation of antiphospholipid antibodies in patients with venous thromboembolism. 1922 Nov

Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibody (AAb) to phospholipid (PL)-binding proteins, such as beta2-glycoprotein I (beta2GPI), and clinical manifestations including thrombosis and/or recurrent pregnancy loss. beta2GPI-reactive T cells are clearly implicated in the generation of these AAb, but the mechanism responsible for their activation remains unclear. We hypothesized that immunization of mice with human beta2GPI, in the context of a potent innate immune activator lipopolysaccharide (LPS), would generate not only high titers of anti-PL AAb, but also a strong beta2GPI-specific T cell response. Healthy, nonautoimmune C57BL/6 mice were immunized repeatedly with human beta2GPI in the presence of LPS. High titers of anti-PL to beta2GPI appeared after the second immunization, with T cell reactivity to beta2GPI detectable only after the fourth immunization. Splenic T cells from these mice proliferated in response to native beta2GPI, alone or bound to anionic PL. These T cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, indicating a Th1 bias of the beta2GPI-specific response. These findings suggest that T cells responsive to beta2GPI may become activated in APS patients by exposure to their cognate Ag in the context of innate immune activation and a pro-inflammatory environment.
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PMID:T cells demonstrate a Th1-biased response to native beta2-glycoprotein I in a murine model of anti-phospholipid antibody induction. 1981 Dec 80

The antiphospholipid syndrome (APS) is a severe autoimmune disease associated with recurrent thrombosis and fetal loss and characterized by the presence of circulating autoantibodies (aAbs) mainly recognizing the N-terminal domain (DmI) of beta2-glycoprotein I (beta2GpI). To possibly block anti-beta2GpI Abs activity, we synthesized the entire DmI comprising residues 1-64 of beta2GpI by chemical methods. Oxidative disulfide renaturation of DmI was achieved in the presence of reduced and oxidized glutathione. The folded DmI (N-DmI) was purified by RP-HPLC, and its chemical identity and correct disulfide pairing (Cys4-Cys47 and Cys32-Cys60) were established by enzymatic peptide mass fingerprint analysis. The results of the conformational characterization, conducted by far- and near-UV CD and fluorescence spectroscopy, provided strong evidence for the native-like structure of DmI, which is also quite resistant to both Gdn-HCl and thermal denaturation. However, the thermodynamic stability of N-DmI at 37 degrees C was remarkably low, in agreement with the unfolding energetics of small proteins. Of note, aAbs failed to bind to plates coated with N-DmI in direct binding experiments. From ELISA competition experiments with plate-immobilized beta2GpI, a mean IC(50) value of 8.8 microM could be estimated for N-DmI, similar to that of the full-length protein, IC(50)(beta2GpI) = 6.4 microM, whereas the cysteine-reduced and carboxamidomethylated DmI, RC-DmI, failed to bind to anti-beta2GpI Abs. The versatility of chemical synthesis was also exploited to produce an N-terminally biotin-(PEG)(2)-derivative of N-DmI (Biotin-N-DmI) to be possibly used as a new tool in APS diagnosis. Strikingly, Biotin-N-DmI loaded onto a streptavidin-coated plate selectively recognized aAbs from APS patients.
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PMID:Chemical synthesis and characterization of wild-type and biotinylated N-terminal domain 1-64 of beta2-glycoprotein I. 2044 Aug 42

The antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL) in the plasma of patients with vascular thrombosis, recurrent complications of pregnancy, or both (1, 2). The presence of aPL in plasma of patients can be detected with either a prolongation of phospholipid dependent coagulation tests (lupus anticoagulant, LAC), or with solid phase immune assays against the protein beta2-glycoprotein I (beta2-GPI) or the phospholipid cardiolipin (anti-beta2-GPI antibody ELISA and anti-cardiolipin antibody ELISA, respectively) (3). For a long time there was a lot of confusion on who had the syndrome and who not. To solve this dispute, an international consensus meeting was organized in Sapporo in 1999 to formulate classification criteria for patients with the antiphospholipid syndrome (4). These criteria have been updated in 2004 at another international consensus meeting in Sydney (5). The classification criteria were defined for scientific purposes and were aimed to be used as inclusion criteria in patient related studies. They were specifically not defined for diagnostic purposes. However, current practice is that these criteria are used as a diagnostic tool. This is very unfortunate because the specificity of the different aPL assays to detect the clinical manifestations that characterize APS are disputable. One of the aims of defining the criteria was to initiate studies to determine the value of the different anti-phospholipid antibody assays to serve as biomarker for the risk of thrombosis and pregnancy morbidity. The recent progress made on this important topic will be discussed.
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PMID:Antiphospholipid syndrome. Current insights into laboratory diagnosis and pathophysiology. 2068 Feb 33


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