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)

The antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) in patients with thromboembolic complications. In APS, most aPL are autoantibodies to beta2-glycoprotein I and prothrombin, which play a major role in the APS pathogenesis. Nevertheless, antibodies with the same antigen specificity are also found in aPL patients with leprosy, in whom thromboembolic complications are uncommon. The in vivo upregulation of the tissue factor (TF) pathway and the imbalance of cytokines have been proposed as potential mechanisms of thrombosis in the APS. We measured the circulating levels of TF, interleukin 6 (IL-6), IL-6 receptor (sIL-6R), tumor necrosis factor (TNF-alpha) and interferon gamma (IFN-gamma) in 83 patients with autoimmune aPL (42 with and 41 without clinical features of definite primary APS), 48 leprosy patients (33 with aPL) and 48 normal controls. There was a trend (P = 0.06) to higher median sTF in patients with autoimmune aPL (139 pg/mL) compared with leprosy patients (103.5 pg/mL) and controls (123 pg/mL). In addition, the frequency of raised sTF levels (> 187 pg/mL) was significantly higher in the group with autoimmune aPL [22.9% (APS 21.4%, non-APS 24.4%)] but not in leprosy (10.4%) compared with controls (4.2%). Elevated levels of IL-6 and TNF-alpha and a trend to lower IFN-gamma were found in patients with definite APS. Leprosy patients with aPL, however, had increased TNF-alpha and IFN-gamma but normal IL-6 levels. Levels of sIL-6R did not differ between controls and either patients with autoimmune aPL or leprosy. The different cytokine profiles as well as differences in circulating levels of TF might contribute to the high thrombotic risk found in patients with autoimmune aPL but not in leprosy related aPL patients.
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PMID:Circulating levels of tissue factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies. 1575 17

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.
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PMID:A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis. 1594 13

We evaluated the prevalence of anti-beta2-glycoprotein I (a-beta2-GPI), anti-phosphatidylserine/prothrombin (a-PP), anti-prothrombin (a-PT), and anti-oxidised low-density lipoprotein (a-oxLDL) antibodies in a cohort of patients with a recent thrombotic event. Among consecutive sera sent to an autoimmune laboratory for routine testing for anti-cardiolipin antibodies (aCL) 473 were found positive for IgG and/or IgM aCL. The referring physicians were requested for clinical information about thrombo-embolic events occurring within 6 months prior to testing. One hundred and sixty-three individuals of which 82 had suffered from cerebro-vascular infarction and 49 from deep venous thromboses or pulmonary emboli were included in the study. Ninety-four sera were positive for IgG aCL and 69 were negative. There was a strong correlation between the presence of IgG aCL and the three other phospholipid-related antibodies: a-beta2-GPI, a-PP, and a-PT. However, IgG a-oxLDL antibodies were almost equally distributed among sera positive and negative for IgG aCL. The presence of antibodies of all subgroups was most pronounced among patients with venous thrombo-embolic disease. In this cohort antibodies to beta2-GPI, PP, PT seem to coexist with aCL. However, a-oxLDL antibodies appear to define a subset of patients, who were older, had more arterial vascular disease, and with no apparent association to the presence of IgG aCL.
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PMID:Prevalence of antibodies against oxidised LDL in a cohort of 163 patients with positive anti-phospholipid antibodies and recent thrombosis. 1618 53

The antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy morbidity in the presence of antiphospholipid autoantibodies (aPL). aPL are a heterogeneous family of autoantibodies with diverse cross-reactivities whose origin and role have not been fully elucidated. Many of the autoantibodies associated with APS are directed against phospholipid-binding plasma proteins, such as beta2-GPI and prothrombin, or phospholipid-protein complexes. The mechanisms by which aPL cause thrombosis are not completely understood. There is no unique mechanism able to explain all symptoms associated with the presence of aPL. Different theories have been proposed, including the effect of aPL on endothelial cells, monocytes, and platelets. aPL are able to recognize, injure, or activate cultured vascular endothelial cells. Cultured endothelial cells incubated with aPL express increased levels of cell adhesion molecules and tissue factor (TF), an effect mediated by beta2-GPI, and may promote inflammation and thrombosis. Overexpression of TF has been also shown in monocytes in vitro and ex vivo. TF is the major initiator of coagulation in vivo; thus, its dysregulation may be one of the most important contributors to thrombosis. Effects of aPL upon platelets are not completely elucidated. aPL bind anionic phospholipid but they are normally in the inner side of cell membranes. When platelets are activated by different agonists, anionic phospholipids are exposed. There is some evidence showing that activated platelets are present in aPL-positive patients. Increased levels of beta-thrombomodulin, and microvesicle formation seem to support this hypothesis. Activated platelets may contribute to thrombosis by persistent exposure of a procoagulant surface.
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PMID:Antiphospholipid-mediated thrombosis: interplay between anticardiolipin antibodies and vascular cells. 1644 33

In an effort to clarify the clinical significance of anti-phospholipid antibodies (aPL) detected by enzyme-linked immunosorbent assay (ELISA), we examined the prevalence of anti-cardiolipin antibodies (aCL), anti-beta2-glycoprotein I antibodies (anti-beta2-GPI), antiprothrombin antibodies (anti-PT), and anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT) in 175 patients with systemic lupus erythematosus (SLE) comprising 67 patients with thrombotic complications. The present study showed that positive results of anti-beta2-GPI-ELISA and anti-PS/PT-ELISA could serve as markers of thrombotic complications in patients with SLE, whereas aCL and anti-PT are less reliable as markers of these complications. Furthermore, results of the anti-PS/PT-ELISA correlate best with the occurrence of both arterial and venous thrombosis in patients with SLE.
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PMID:The presence of anti-phosphatidylserine/prothrombin antibodies as risk factor for both arterial and venous thrombosis in patients with systemic lupus erythematosus. 1662 57

Antiphospholipid syndrome (APS) is an autoimmune disorder in which vascular thrombosis and recurrent pregnancy loss occur in patients with antiphospholipid antibodies(aPL). Measurements of the beta2-glycoprotein I-dependent anticardiolipin antibody(aCL) and lupus anticoagulant(LAC) are the only laboratory tests available for the diagnosis of APS. Recently, phosphatidylserine-dependent antiprothrombin antibody(aPS/PT) has been detected. aPS/PT was measured by ELISA using the phosphatidylserine-prothrombin complex as an antigen immobilized on ELISA plates in the presence of CaCl2. In our study of 219 patients with APS and autoimmune diseases, the prevalence of aPS/PT-IgG in those with APS was 42.2%, which was significantly higher than that(4.6%) in patients with autoimmune diseases. Furthermore, aPS/PT was closely associated with APS manifestations with an odds ratio (OR) of 2.92 (95% confidence interval (95% CI): 1.33 to approximately 6.40), whereas the OR for aCL was 2.06 (95% CI: 0.91 to approximately 4.66). In addition, aPS/PT-IgG was strongly correlated with the presence of LAC as detected with a diluted Russell viper venom time test (dRVVT) (OR: 38.2, 95% CI: 13.4 to approximately 109.1). The monoclonal antibody (23-1D) of aPS/PT also prolonged the clotting time in LAC tests (aPTT, dRVVT, and kaolin clotting time) in a concentration-dependent manner. In conclusion, aPS/PT is more closely associated with manifestations of APS and LAC, and positive results from an aPS/PT test can mark thrombotic events in APS patients. The determination of aPS/PT in clinical practice, in conjunction with that of other aPL, may improve the likelihood of recognizing APS.
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PMID:[Phosphatidylserine-dependent anti-prothrombin antibody as a new marker for the diagnosis of antiphospholipid syndrome]. 1663 74

We clarified the clinical significance of IgG anti-phosphatidylserine-prothrombin complex (PS-PT) antibodies in the antiphospholipid syndrome (APS). The study population consisted of 122 patients with SLE and lupus-like disease. IgG anti-PS-PT antibodies were detected in 44% of 59 patients according to the diagnostic criteria by Harris and Hughes. This frequency was significantly (p < 0.005) higher than the 14% seen in patients without APS. IgG anti-PS-PT antibodies were strongly (p < 0.005) associated with thrombosis. In addition, IgG anti-PS-PT antibodies were positive in 64% of IgG beta2-GPI dependent anti-cardiolipin antibody negative APS patients under the Sapporo criteria. The above findings indicate that IgG anti-PS-PT antibodies as well as beta2,-GPI dependent anti-cardiolipin antibodies should be examined in the diagnosis of APS.
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PMID:[Clinical significance of anti-phosphatidylserine-prothrombin complex antibodies in antiphospholipid syndrome]. 1670 13

Antibodies against prothrombin are detected by enzyme immunoassays (EIA) in sera of patients with antiphospholipid syndrome (APS). However, there are two methods for antiprothrombin EIA; one that uses high binding plates (aPT-A), and another that utilizes phosphatidylserine bound plates (aPS/PT). We aimed to evaluate and compare aPT-A and aPS/PT in a clinical setting. We performed EIA for anti-PT, anti-PS/PT, IgG, and IgM anticardiolipin antibodies (aCL), and IgG beta2-glycoprotein I-dependent aCL (abeta2GPI/CL) with serum samples from 139 systemic lupus erythematosus (SLE) patients (16 with history of at least one thrombotic episode) and 148 controls. We observed that: (1) although titers of anti-PT and anti-PS/PT were significantly related with each other (P < 0.0001, rho = 0.548), titer of anti-PT and anti-PS/PT differed greatly in some samples; (2) odds ratio and 95% confidence interval for each assay was 3.556 (1.221-10.355) for aPT-A, 4.591 (1.555-15.560) for aPS/PT, 4.204 (1.250-14.148) for IgG aCL, 1.809 (0.354-9.232) for IgM aCL, and 7.246 (2.391-21.966) for abeta2GPI/CL. We conclude that, while all EIA performed in this study except IgM aCL are of potential value in assessing the risk of thrombosis, aPS/PT and abeta2GPI/CL seemed to be highly valuable in clinical practice, and that autoantibodies detected by anti-PT and anti-PS/PT are not completely identical.
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PMID:Significance of antiprothrombin antibodies in patients with systemic lupus erythematosus: clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine/prothrombin assay, and comparison with other antiphospholipid antibody assays. 1676 54

The concurrence of antiphospholipid (aPL) antibodies and thrombosis or pregnancy loss defines the 'antiphospholipid syndrome' (APS). The Sydney update of the classification criteria for definite APS diagnosis introduced numerous ameliorations to the previous preliminary consensus statement. Clinical criteria are now better defined as vascular thrombosis must be diagnosed on the basis of objective criteria. Moreover,additional risk factors for thrombosis or pregnancy loss must be taken into account before the diagnosis is made and should be described in detail in scientific reports. As far as laboratory criteria are concerned,the lack of standardization and the misinterpretation of results remain major problems often leading to overdiagnosis. A single positive test result out of the possible assays determining aPL antibodies (Lupus Anticoagulant, LAC, anticardiolipin, aCL and anti. beta2-Glycoprotein I, beta2-GPI, antibodies) is still sufficient,according to the Sydney criteria, to justify a diagnosis of APS. Nevertheless single test positivity may result in overdiagnosis or identification of low risk patients and use of all three tests seems more reasonable. Multiple positivity or (better) triple positivity in our experience allows for the identification of high risk patients for possible recurrence. In the near future, coagulation tests discriminating between a beta2-GPI and anti-prothrombin LAC may be useful in identifying high risk patients.
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PMID:The diagnosis of the antiphospholipid syndrome. 1685 67

The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (beta2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.
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PMID:Current concepts on the pathogenesis of the antiphospholipid syndrome. 1698 76


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