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)

Antibodies to beta2-glycoprotein I (anti-beta2GPI) have been associated with recurrent thrombosis and pregnancy morbidity. However, the prevalence of anti-beta2GPI in children suffering from cerebral infarction is unknown. We report on a 20-month-old boy who had an ischemic stroke, secondary to antiphospholipid syndrome with high titers of immunoglobulin G anti-beta2GPI (first titer: 132 U; second titer 6 weeks later: 350 U; normal range: 0-100 U). Anticardiolipin antibodies and lupus anticoagulant tests were negative. All other causes of infarction were excluded. Laboratory studies showed anti-beta2GPI IgG levels of 164 U and 216 U at 6 months and 2 years, respectively, after the onset. The patient received treatment with low-dose aspirin. To our knowledge, this is the first reported case of childhood ischemic stroke with only anti-beta2GPI but no antibodies detectable in standard antiphospholipid assays. This case supports the recommendation of others to search for these antibodies in the presence of strong clinical suspicion of antiphospholipid syndrome, when anticardiolipin antibodies and lupus anticoagulant tests are negative.
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PMID:Anti-beta2-glycoprotein I antibodies and ischemic stroke in a 20-month-old boy. 1283 87

Antiphospholipid antibodies are commonly found in patients with systemic lupus erythematosus or the antiphospholipid syndrome, and a subset of such antibodies is associated with prothrombotic events such as stroke and with adverse pregnancy outcomes and fetal loss. We examined sera from 411 patients who were clinically characterized as to their periodontal disease status for serum levels of beta2-glycoprotein I-dependent anti-cardiolipin autoantibodies (anti-CL). The prevalence of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) positive for anti-CL (16.2% and 19.3%, respectively) was greater than that in healthy controls (NP) and localized aggressive periodontitis (LAgP) patients (6.8% and 3.2%). Patients with these autoantibodies demonstrated increased pocket depth and attachment loss compared with patients lacking the antibodies. Analysis of the data indicates that patients with generalized periodontitis have elevated levels of autoantibodies reactive with phospholipids. These antibodies could be involved in elevated risk for stroke, atherosclerosis, or pre-term birth in periodontitis patients.
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PMID:Anti-cardiolipin antibodies in sera from patients with periodontitis. 1457 6

Though many neurological deficits have been described in the antiphospholipid syndrome (APS), only stroke is well established and accepted as a diagnostic criterion in this disease. We review clinical data obtained from a large series of cases regarding stroke, dementia, epilepsy, chorea, migraine, white matter disease and behavioral changes in APS or linked to laboratory criteria such as antiphospholipid antibodies (aPL). The contribution of animal models to our understanding of these manifestations of APS is stressed, especially regarding the cognitive and behavioral aspects for which we have established model systems in the mouse. These models utilize immunization of mice with beta2-glycoprotein I, a central autoantigen in APS, which induces persistent high levels of aPL. These mice develop hyperactive behavior after a period of four to five months as well as deficits in learning and memory and are potentially valuable as a system in which to study the pathogenesis and treatment of cognitive and behavioral aspects of APS. Another model we have developed, in which IgG from APS patients induce depolarization of brain synaptoneurosomes, may serve as a model for the pathogenesis of epilepsy in APS.
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PMID:CNS dysfunction in the antiphospholipid syndrome. 1471 9

Antiphospholipid syndrome is considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack. Antiphospholipid antibodies (aPL) comprise a heterogeneous group of autoantibodies. Among them, lupus anticoagulant (LA) and beta 2-glycoprotein I dependent anticardiolipin antibody (beta 2-GPI aCL) are important and commonly measured. Recently, LA has been considered to be closely related to phosphatidylserine anti-prothrombin antibody. APL is an independent risk factor for first-ever ischemic stroke and a prognostic marker of recurrent stroke. The precipitating factors for the occurrence of stroke are the presence of beta 2-GPI-dependent aCL, a GPL aCL level of more than 40, and the simultaneous presence of lupus anticoagulant. Several mechanisms are believed to be involved in the thrombotic process in patients with antiphospholipid antibodies. Human activated protein C functions as a potent anticoagulant in human plasma by inhibiting the activity of coagulation cofactors Va and VIIIa. Activation of protein C is impaired in patients with aPL. Recently, the presence of aPL has been considered to be contributory factor for the development of atherosclerotic lesions. Transgenic mouse lacking the LDL receptor develop accelerated arteriosclerosis upon immunization with beta 2-GPL Several therapeutic options are available for the prevention of ischemic stroke in patients with aPL, such as antiplatelet, anticoagulant, and immunosuppressive therapy. The rate of recurrence in patients undergoing antiplatelet and anticoagulation combination therapy was found to be lower than that in patients receiving other forms of therapy. The WARSS-APASS collaborative study showed that there was no difference in the recurrence rate between aPL patients receiving antiplatelet or anticoagulation therapy alone. APL has been investigated in other neurological disorders such as multiple sclerosis, chorea, migraine and convulsion. The association of aPL with multiple sclerosis remains debatable. APL could be a contributory factor for the development of convulsion, but not for migraine.
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PMID:[Neurological aspects in antiphospholipid syndrome]. 1515 54

The study of IgG and IgM anti-cardiolipin antibodies (IgG/IgM aCL) is now well accepted and is routinely used in the risk assessment of various conditions associated with thrombosis. The aim of the study was to define whether the investigation of aCL is sufficient by itself to evaluate a risk of ischemic stroke. Frequency of aCL and anti-beta2-glycoprotein I (beta2-GPI) antibodies was prospectively investigated in 96 patients with ischemic stroke and in 119 controls by ELISA. In ischemic stroke patients IgG aCL were found in 36%, the IgM-aCL were found in 58%, the IgG-IgM-aCL were found in 43%. The levels of both antibodies were higher in patients with ischemic stroke than in controls (p < 0.01). In controls, IgM-aCL were positive in 2% and IgG-aCL antibodies were negative. IgG-beta-GPI Abs were found in ischemic patients in 19% and IgM-beta2-GPI Abs in 37%. The IgG-IgM-anti-beta2-GPI Abs were found in 24% patients. They were negative in controls. There was a correlation between levels of aCL and anti-beta2-GPI Abs for both isotypes (r = 0.728) but not between IgG- and IgM-beta2-GPI Abs. IgG-aCL test was more sensitive for ischemic stroke than the IgG-beta2-GPI Abs test (71.4%, respectively 65.7%) but less specific (66.8%, respectively 88.6%). The sensitivity of anti-beta2-GPI Abs for ischemic stroke was increased when both isotypes were tested. These results showed that aCL and anti-beta2-GPI Abs could be pathogenetically important for ischemic stroke and that anti-beta2-GPI Abs testing might contribute to a better evaluation of ischemic stroke.
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PMID:Study of anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with ischemic stroke. 1552 3

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

Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.
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PMID:2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005. 1633 12

Antiphospholipid syndrome is characterized by arterial or venous thrombosis, and the presence of antiphospholipid antibodies (aPL). APL are considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack (TIA). We examined the causes in 50 young patients with ischemic stroke. The most prevalent cause was atherosclerosis and the incidence of APS was 12.5%. APL comprise a heterogeneous group of autoantibodies, such as beta2-glycoprotein I dependent anticardiolipin antibody (beta2-GPIaCL), lupus anticoagulant (LA), and other antiphospholid-protein antibodies. We examined the incidence and the pathogenic role of antiphospholipid protein antibodies. The subjects comprised 250 patients (155 male, 95 females) with ischemic stroke, aged 26 to 92 years (mean 72 years). We measured beta2-GPI aCL, IgG aCL, LA, phosphatidyserine dependent antiprothrtombin antibody (PS-PT), antiphosphatidyl-serine antibody (PS), antiphosphatidyl-inositol antibody (PI) in each patient. The incidence of beta2-GPI aCL, IgG aCL, LA, phosphatidyserine, PS-PT, PS, and PI was 2.8%, 12%, 9.2%, 7.2%, 9.6%, and 8.8%, respectively. The incidence of young stroke patients under 50 years was 5.2%. Among 13 young stroke patients, 5 had SLE. Among 23 patients with LA., 18 (78%) patients had PS-PT. Anti-PS-PT antibody is closely related to LA. Antinuclear antibody was detected in 79% of the patients with aPS and/or aPI. We compared the carotid ultrasonographic findings in positive aPI or aPS patients with those in negative ones. Increased IMT, plaque score and carotid stenosis were more common in aPI and aPS-positive patients than in negative ones Three of 5 patients who showed positive beta2-GPI, aCL and LA, simulataneously, had sysyemic lupus erythematosus as an immulological background. Two of 3 patients with PI and/or PS and beta2-GPI and/or LA were patients with SLE. Antiphospholipid antibody was considered to be a risk factor of stroke, especially in SLE and/or young female patients. The incidence of lupus anticoagulant is more common than beta2-GPI aCL in ischemic stroke. In SLE patients with stroke, multi-antiphospholipid-protein antibodies was inclined to be present. LA is closely related to ant-PS-PT and aPI and aPS are associated with anti-nuclear antibody and precipitation of atherosclerosis.
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PMID:[Antiphospholipid syndrome and stroke]. 1644 44

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

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


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