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)

Amendments to the Sapporo criteria for the diagnosis of the antiphospholipid syndrome (APS) have recently be published and include testing for the presence of IgG and IgM beta2-glycoprotein I (beta(2)GPI) antibodies. The Asserachrom Antiphospholipid antibodies line (Diagnostica Stago) with a monoclonal based standardisation, was evaluated in a Lupus anticoagulant (LAC) positive (n = 138) and a LAC negative (n = 134) populations. The ELISA line consists of the Asserachrom APA Screen, the Asserachrom APA IgG,M and the Asserachrom anti-beta(2)GPI IgG and IgM. Anti-prothrombin antibodies (APT), not being included in the updated laboratory criteria, have been tested by the Asserachrom anti-prothrombin IgG,M. Imprecision characteristics showed coefficients of variation (CV) ranging from 4.9% to 13.9%. Cut-off values were calculated with the 99 percentile. The Asserachrom APA Screen showed 1,5% false positive and 0,7% false negative results in correlation with the Asserachrom APA IgG,M. 14.7% of the patients were positive for beta2GPI antibodies, 30,0% of them showed a negative Asserachrom APA Screen. beta(2)GPI antibodies may be the only test positive in a minority of patients, so the Asserachrom APA Screen and the Asserachrom anti-beta(2)GPI IgG and IgM should be performed in parallel when APS is suspected. LAC and APA assays, however, remain essential in the laboratory diagnosis of APS.
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PMID:Evaluation of new commercial enzyme-linked immunosorbent assay kits in the laboratory diagnosis of antiphospholipid syndrome in view of the revised classification criteria of the antiphospholipid syndrome. 1710 52

The immunolocalization of oxidized low-density lipoproteins (ox-LDL), beta2-glycoprotein I (beta(2)GPI), CD4(+)/CD8(+) immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox-LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox-LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme-linked immunosorbent assays (ELISAs) to measure circulating ox-LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox-LDL interacts with beta(2)GPI and circulating ox-LDL/beta(2)GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that beta(2)GPI binds ox-LDL to neutralize its proinflammatory and proatherosclerotic effects. Because beta(2)GPI is ubiquitous in plasma, its interaction with ox-LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox-LDL/beta(2)GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox-LDL.
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PMID:Determination of oxidized low-density lipoproteins (ox-LDL) versus ox-LDL/beta2GPI complexes for the assessment of autoimmune-mediated atherosclerosis. 1778 19

Beta(2)-glycoprotein-I (beta(2)-GPI, also known as apolipoprotein H) is a major autoantigen in the antiphospholipid syndrome (APS), a disease commonly affecting the central nervous system. We examined whether beta2-GPI and similar proteins exist in rat and human brains. No expression was found on Northern blot analysis of human brain. Utilizing a standard procedure for the isolation of serum beta2-GPI we purified a 100 kD human brain protein, which was found by peptide sequencing to have full homology with the serum protein, histidine-rich glycoprotein (HRGP). Expression of HRGP in rat and human brain was established by RT-PCR studies and a partial sequence of rat brain HRGP was obtained showing 68% homology with the human protein. IgG from most APS patients bound to HRGP, which shares distinct biochemical properties with beta2-GPI, is present in the brain and may be an important autoantigen.
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PMID:Identification of histidine-rich glycoprotein, a potential autoantigen, in human and rat brain preparations. 1778 36

The discovery that antiphospholipid antibodies recognize plasma proteins that bind to phospholipids rather than recognizing phospholipids themselves has been a major advance in research into antiphospholipid syndrome (APS). It is now established that beta2-glycoprotein I (beta2 GPI) is the most important antigen for antiphospholipid antibodies. However, the possible pathologic mechanism is still much debated. This is mainly because not all patients with anti-beta2 GPI antibodies show clinical symptoms that are related to APS. Several reports indicate that anti-beta2 GPI antibodies with lupus anticoagulant (LA) activity are clinically of much importance. Most patients with LA caused by anti-beta2 GPI antibodies suffer from thrombosis as a result of recognition of the first domain of beta2 GPI by these antibodies. In the search for a pathologic mechanism that might explain the high occurrence of thrombosis in patients with anti-domain I antibodies (LA-causing anti-beta2 GPI antibodies), it was found that these antibodies show increased resistance to the anticoagulant activity of annexin A5. We have shown that the same population of antibodies also displays increased resistance to activated protein C. Owing to the diversity of clinical symptoms related to APS, it is likely that other pathologic mechanisms also contribute to the occurrence of APS-related symptoms.
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PMID:Mechanisms of disease: antiphospholipid antibodies-from clinical association to pathologic mechanism. 1828 65

The antiphospholipid syndrome (APS) is an acquired thrombophilia, characterized by the occurrence of venous and arterial events. This article examines the laboratory and key clinical aspects of APS. Particular focus is given to anti-beta 2-glycoprotein I (beta(2)GPI) antibodies in view of their recent inclusion in the APS classification criteria. The clinical utility of using the beta(2)GPI enzyme-linked immunosorbent assay, in conjunction with the established lupus anticoagulant assays and cardiolipin enzyme-linked immunosorbent assay, for diagnosing and risk stratifying patients suspected of having APS is discussed. The relative importance of the various assays in diagnosing obstetric APS (early and late gestation miscarriages) is explored. The implications of recent epidemiologic findings for possibly understanding the underlying pathophysiologic mechanisms of obstetric APS are highlighted. Insights into which patients with obstetric APS may be at most risk of thrombotic complications are presented.
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PMID:How we diagnose the antiphospholipid syndrome. 1875 86

In the antiphospholipid syndrome (APS), pathogenic antiphospholipid antibodies (aPL) that cause thrombosis or pregnancy morbidity are characterized by binding to anionic phospholipids (PL) and beta2-glycoprotein I (beta(2)GPI). Sequence analysis of human monoclonal aPL has shown that high affinity for these antigens is associated with the presence of three particular amino acids: arginine (Arg), asparagine and lysine in the complementarity determining regions (CDRs) of their heavy and light chains. In vitro expression systems have been used to create variants of the antibodies in which these amino acids have been altered. In general, removal of Arg residues reduces affinity for anionic PL and beta(2)GPI. Arg at different positions in the sequence, however, have different effects on binding affinity and effects on binding are not always mirrored by effects on pathogenicity. This review will focus upon the sequence motifs that have been found to distinguish pathogenic from non-pathogenic aPL, and whether these or other properties may help to identify distinct pathogenic subsets of aPL. In particular, we will focus on our recent work in which we are trying to develop a better understanding of the molecular mechanisms involved in activation of target cells by pathogenic aPL. These studies, together with molecular models of antigen/antibody complexes, help us to understand exactly how pathogenic antibodies interact with antigens. Ultimately, this understanding may aid the design of more powerful diagnostic/prognostic assays and targeted therapeutic agents to block the pathogenic effects of these antibodies.
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PMID:Examining the non-linear relationship between monoclonal antiphospholipid antibody sequence, structure and function. 1882 54

Antiphospholipid syndrome is considered to be associated with a hypercoagulable state that leads to stroke and other ischemic events, and is currently diagnosed based on the modified Sapporo criteria that was proposed in 2006. Antiphospholipid antibodies (aPL) comprise a heterogeneous group of autoantibodies. Among them, the level of beta2-glycoprotein I-dependent anticardiolipin antibody, lupus anticoagulant (LA), and IgG anticardiolipin antibody are commonly measured. Recently, phosphatidylserine dependent anti-prothrombin antibody has been suggested to be closely related to LA. aPL is an independent risk factor for a first-ever ischemic stroke, especially in young female patients. It is still debatable whether aPL is a marker for recurrent stroke risk. The precipitating factors for the occurrence of stroke are beta2-GPI-dependent aCL, aGPL, and aCL levels of greater than 40, and the simultaneous presence of LA. Several mechanisms are considered to be involved in the thrombotic process in patients with antiphospholipid antibodies. Activation of protein C is impaired in patients with aPL. Beta2-GPI has simultaneous procoagulant and anticoagulant effects. Cardiac valvular involvement, which could be the cause of cardiogenic embolism, is prevalent in patients with aCL. In addition, the presence of aPL is associated with the development of atherosclerosis. Recently, it has been proposed that endothelial cells, monocytes, and platelets were reported to be activated by beta2-GPI: further, p38 mitogen-activated protein kinase has been reported to be phosphorylated. Several therapeutic options are available for the prevention of ischemic stroke in patients with aPL. For cases of cryptogenic ischemic stroke and positive aPL antibodies, antiplatelet therapy is reasonable. Oral anticoagulation with a target international normalized ratio (INR) of 2 to 3 is reasonable for patients with ischemic stroke who meet the criteria for antiphospholipid syndrome with venous and arterial occlusive disease in multiple organs.
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PMID:[Ischemic stroke with antiphospholipid antibody]. 1897 2

Prothrombin (PT) is a target for antibodies with lupus anticoagulant (LA) activity. Anti-prothrombin antibodies (aPT) were recently identified as antibodies directed toward a phospholipid-binding protein. aPT are a new serologic marker of antiphospholipid syndrome. The objective was to detect aPT in a group of 46 patients with acute ischemic stroke in order to correlate their presence with clinical diagnosis, laboratory and neuroradiological findings. We tested aPT, lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-bbeta2-GPI) in 46 young women with acute ischemic stroke aged 34-45 years and 43 patients with nonischemic neurologic diseases and 141 normal controls. Anti-prothrombin antibodies were detected by calcium-containing aPT ELISA, aCL and anti-beta2-GPI by ELISA. All samples were screened using the activated partial thromboplastin time (aPTT); the dilute Russell viper venous time (dRVV) coagulation test was performed. The results were statistically analyzed. Anti-prothrombin antibodies were found in 26 (57%) of 46 stroke patients. Out of 43 patients with nonischemic neurological disorders, 2 (4.18%) were positive for aPT. aPT were detected in one (0.70%) of the normal controls. Ten stroke patients (21%) were positive for IgG aPT only, 9 stroke patients (18.2%) for IgM aPT only, and 8 stroke patients (16.9%) for both IgG and IgM isotypes of aPT. Two nonischemic neurological disorders patients (4.18%) presented IgM isotype of aPT. Patients with ischemic stroke presented aPT much more frequently than the healthy controls (OR 182.00 [95% CI 23.382-1416.6]. p < 0.0001). Patients with ischemic stroke presented aPT much frequently than the nonischemic neurological disorders patients (OR 26.650 [95% CI 5.743-123.66], p < 0.0001). When IgG or IgM aPT were considered separately, they were more frequently found in patients with ischemic stroke than in healthy control group (OR 38.889 [95% CI 4.817-313.95], p < 0.0001) and (OR 34.054 [95% CI 4.178-277.5], p < 0.0001), respectively. Simultaneous positive titers for both isotypes of aPT (IgG and IgM) were more frequently found in patients with ischemic stroke than in healthy control group (OR 29.474 [95% CI 3.573-243.12], p < 0.0001). Eleven stroke patients (43%) were negative for aCL, LA and anti-beta2-GPI, but positive for aPT (OR 0.03287 [95% CI 0.001794-0.6022], p < 0.001). aCL, LA and anti-beta2-GPI were not found both in nonischemic neurological disorders patients and in healthy controls.
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PMID:Detecting anti-prothrombin antibodies in young women with acute ischemic stroke. 1948 Mar

Growing evidence suggests that autoantibodies directly contribute to hypercoagulability in the antiphospholipid syndrome (APS). One proposed mechanism is the antibody-induced expression of tissue factor (TF) by blood monocytes. Annexin A2 (ANX2), a mediator of cell surface-specific plasmin generation, was identified to mediate endothelial cell activation by anti-beta2-glycoprotein I (anti-beta 2 GPI) antibody. Our previous study suggested that ANX2 was also involved in anti-beta 2 GPI/beta 2 GPI-induced TF expression on monocytes. In the current study, it was further demonstrated that beta 2 GPI interacts with ANX2 not only in a cell-dependent form but also in a cell-free system. To further confirm the effects of ANX2 on anti-beta 2 GPI/beta 2 GPI-induced TF expression, an ANX2 cDNA-containing vector was transfected into HEK 293T cells which had originally little ANX2, then cells were treated by anti-beta 2 GPI/beta 2 GPI complex. It was found that transfected HEK 293T cells could express more TF both at mRNA and protein levels than that of no-transfected cells. On the other hand, the TF expression was dramatically decreased in the THP-1 cells in which the ANX2 RNA interference was performed. In conclusion, these results indicate that ANX2 on cell surface functions as a mediator boosting TF expression on monocytes induced by anti-beta 2 GPI/beta 2 GPI complex, which is contributed to the thrombotic events in APS.
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PMID:Annexin A2 mediates anti-beta 2 GPI/beta 2 GPI-induced tissue factor expression on monocytes. 1972 97

Abnormalities of the lipid profile partly explain the atherogenic tendency of systemic lupus erythematosus but the picture is unclear in thrombotic primary antiphospholipid syndrome (PAPS). Herein we compare the lipid profile, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein A (ApoA-I), apolipoprotein B (ApoB), triglycerides (TRY)), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-ss(2)GPI) and C-reactive protein (CRP) from thrombotic PAPS (n = 34), thrombotic patients with inherited thrombophilia (IT; n = 36), subjects persistently positive for antiphospholipid antibodies (aPL, n = 18) with no underlying autoimmune or non-autoimmune disorders and healthy controls (n = 28) and determined the reciprocal effects of anti-lipoprotein antibodies, the lipid profile, oxLDL-ss(2)GPI and CRP. Average concentrations of HDL (p < 0.0001), LDL (p < 0.0001), CHO (p = 0.0002), ApoA-I (p = 0.002) were lower in PAPS whereas average TRY was higher (p = 0.01) than other groups. Moreover, the aPL and PAPS group showed higher levels of IgG anti-HDL (p = 0.01) and IgG anti-ApoA-I (p < 0.0001) whereas the PAPS group showed greater average oxLDL-ss(2)GPI (p = 0.001) and CRP (p = 0.003). Within the PAPS group, IgG anti-HDL correlated negatively to HDL (p = 0.004) and was an independent predictor of oxLDL-ss2GPI (p = 0.009). HDL and ApoA-I correlated negatively with CRP (p = 0.001 and p = 0.007, respectively). IgG anti-HDL may hamper the antioxidant and anti-inflammatory effect of HDL favoring low-grade inflammation and enhanced oxidation in thrombotic PAPS.
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PMID:High-density lipoprotein inversely relates to its specific autoantibody favoring oxidation in thrombotic primary antiphospholipid syndrome. 2006 10


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