Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta 2-glycoprotein I (beta 2-GP I) is a plasma protein with a high affinity for negatively charged surfaces. In vitro this protein shows a variety of anticoagulant properties (inhibition of contact activation and platelet dependent prothrombinase activity). Therefore we studied the possibility that a hereditary beta 2-GP I deficiency is a risk factor for (familial) thrombophilia. Plasma beta 2-GP I levels were measured in healthy volunteers and four different groups of patients with (familial) thrombophilia. In these 5 groups the prevalence of beta 2-GP I deficiency (i.e. beta 2-GP I antigen less than 77%) was found to be very similar (6.8-12.5%) and statistically not significantly different. This observation suggests that beta 2-GP I deficiency in itself is not a risk factor for thrombosis. One thrombophilic patient was found to be homozygous deficient of beta 2-GP I. The transmission of the defect in his family followed autosomal inheritance. One of his brothers was also homozygous deficient and at the age of 35 years still free of thromboembolic complications. The possibility that beta 2-GP I deficiency could be an additional risk factor for the development of thrombophilia in families with protein C deficiency was evaluated in a panel of 70 unrelated patients with clinically dominant protein C deficiency. The prevalence of beta 2-GP I deficiency in this group of patients (12.8%) was very similar to that in other groups of normals and patients. Moreover, there was no difference in the frequency of beta 2-GP I deficiency in symptomatic and asymptomatic protein C deficient patients.
 ...
PMID:Beta 2-glycoprotein I deficiency and the risk of thrombosis. 150 4

It has been reported that antiphospholipid autoantibodies do not recognize phospholipid alone, but rather the plasma protein beta 2-glycoprotein I (beta 2GPI), or a beta 2GPI-phospholipid complex. In vitro beta 2GPI binds to anionic phospholipids and inhibits the prothrombinase activity of procoagulant membranes. In light of the fact that lupus anticoagulants, a type of antiphospholipid antibody, have similar anticoagulant properties, the relationship of beta 2GPI to lupus anticoagulant activity was investigated. IgG from patients with autoimmune diseases or syphilis were tested for anticardiolipin reactivity and lupus anticoagulant activity in the presence and absence of beta 2GPI. As expected, anti-cardiolipin reactivity associated with autoimmune disease was beta 2GPI dependent. In contrast, IgG from a patient with syphilis recognized cardiolipin alone and binding was inhibited by beta 2GPI. Autoimmune antiphospholipid antibodies prolonged the dilute Russell viper venom time of normal plasma, but had no effect on beta 2GPI-depleted plasma. Antiphospholipid antibodies associated with syphilis had no anticoagulant effect. RP-1, an anti-beta 2GPI mAb, had anticoagulant effects similar to those of autoimmune antiphospholipid antibodies. These data demonstrate that antiphospholipid autoantibodies exert lupus anticoagulant activity via an interaction with beta 2GPI. These antibodies and RP-1 appear to amplify the anticoagulant effect of beta 2GPI itself.
 ...
PMID:Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. 152 18

In the present paper the influence of beta 2-glycoprotein-I, also known as apolipoprotein H, upon the prothrombinase activity of platelets and phospholipid vesicles was investigated. The results can be summarized as follows. 1. The prothrombinase activity of resting, non-activated platelets, lysed platelets and vesicles composed of phosphatidylserine and phosphatidylcholine at different molar ratios is inhibited by beta 2-glycoprotein-I in a dose-dependent manner. The concentration of glycoprotein which produces marked inhibition is within the physiological plasma concentration range of beta 2-glycoprotein-I. 2. The time dependence of this inhibition is a relatively slow process, which is not fully expressed before 1 h of incubation. 3. The effect of the glycoprotein is not due to a direct interaction with the components of the prothrombinase complex, i.e. factors Xa, Va, Ca2+ or prothrombin, nor is the inhibitory action abolished by increasing concentrations of coagulation factors Xa and Va. This suggests that beta 2-glycoprotein-I causes a reduction of the prothrombinase binding sites of these coagulation factors to platelets or phospholipid vesicles. 4. The prothrombinase activity of platelets stimulated with ionophore A23187 or with collagen plus thrombin is also inhibited by beta 2-glycoprotein-I in a manner similar to that observed for phospholipid vesicles or for lysed platelets. These findings suggest a regulatory role for beta 2-glycoprotein-I in the pathway of blood coagulation.
 ...
PMID:Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I. 376 9

Antiphospholipid (aPL) antibodies include anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies. LA antibodies recognize the complex of lipid-bound (human) prothrombin, in this way inhibiting the phospholipid-dependent coagulation reactions, whereas aCL antibodies are directed towards beta 2-glycoprotein I (beta 2-GPI) bound to an anionic lipid surface. According to their behavior in coagulation reactions, we have divided aCL antibodies into two groups: aCL-type A, which inhibit the phospholipid-dependent coagulation reactions because they enhance the binding of beta 2-GPI to the procoagulant phospholipid surface; and aCL-type B antibodies, which are devoid of anticoagulant properties. We report the distinctive laboratory and clinical profiles of 25 patients with well-characterized, phospholipid-dependent inhibitor of coagulation. Fourteen patients had LA antibodies (aCL-type B were concomitantly present in 10 cases, while in the other four, aCL titer was normal), and the other 11 had aCL-type A antibodies. The laboratory evaluation of the two groups showed the dilute Russell viper venom time (dRVVT) to be the most abnormal coagulation test in the aCL-type A-positive group, whereas the kaolin clotting time (KCT) was the most abnormal assay in the LA-positive group. In fact, the ratios of the coagulation times of patient plasma over normal pooled plasma (mean +/- standard deviation) for LA versus aCL-type A antibodies were 1.48 +/- 0.27 versus 2.20 +/- 0.42, P = .0001, and 2.22 +/- 0.42 versus 1.50 +/- 0.42, P = .0003, for the dRVVT and KCT, respectively. No differences were observed either in the ratios of the activated partial thromboplastin times and the prothrombin times or the plasma levels of beta 2-GPI and prothrombin. Conversely, aCL titers were significantly higher in aCL-type A-positive patients (147 +/- 44 U) than in the LA-positive group (61 +/- 55 U; P = .0003). We ruled out the possibility that platelet contamination of plasma could account for the observed coagulation profiles, as the two patterns were reproduced in platelet-free plasma. In addition, we performed clotting tests in plasma in the presence of phospholipids and calcium after addition of factor IXa or factor Xa. The assay performed with factor Xa was more sensitive to the presence of aCL-type A antibodies, while the assay performed with factor IXa was preferentially sensitive to LA-containing plasmas, supporting the earlier findings with the dRVVT and KCT assays.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Kaolin clotting time and dilute Russell's viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein I-dependent antiphospholipid antibodies. 760 91

Apolipoprotein H (ApoH) is a 50 kDa glycoprotein capable of binding to negatively charged phospholipids and is a probable inhibitor of the blood coagulation pathway, platelet aggregation, and platelet prothrombinase activity, as well as being involved in autoimmune disease. We have cloned and sequenced a full length ApoH cDNA clone from a beagle dog liver library. Its derived amino acid sequence shows high cross-species similarity to ApoH from other mammals. Canine ApoH mRNA expression is down regulated during an experimentally induced inflammatory response establishing that it is a negative acute phase reactant.
 ...
PMID:Characterization and acute phase modulation of canine apolipoprotein H (beta 2-glycoprotein I). 768 67

We have previously demonstrated that patients with cirrhosis may be positive for lupus anticoagulant and anticardiolipin antibodies. The prevalence and clinical value of antiphospholipid antibodies in cirrhosis have never been described. Besides, it has not yet been determined if serum levels of beta-2-glycoprotein I, which is synthesized by the liver and mediates the interaction between cardiolipin and anticardiolipin antibodies affects lupus anticoagulant detectability in cirrhosis. We evaluated the prevalence of lupus anticoagulant in 63 patients with cirrhosis and related it to beta-2-glycoprotein I serum levels. We also analyzed whether lupus anticoagulant and anticardiolipin antibodies were associated with previous thrombotic complications. Eleven patients (18%) were lupus anticoagulant positive; 14 (22%) had high values of anticardiolipin antibodies. Fourteen patients had a previous history of splanchnic venous thrombosis (n = 9) or thrombophlebitis (n = 5). A significant association between lupus anticoagulant (p = 0.0001), anticardiolipin antibodies (p = 0.0001) and venous thrombosis was found. Patients with severe liver failure had significantly lower beta-2-glycoprotein I levels than those with moderate (p < 0.01) or low (p < 0.001) hepatic insufficiency. Among 14 anticardiolipin antibodies positive patients, six with severe liver failure were lupus anticoagulant negative and had beta-2-glycoprotein I values below 100 micrograms/ml. In four of these, basal values of dilute activated partial thromboplastin time were not modified by the addition of 50 micrograms/ml of exogenous beta-2-glycoprotein I. This study shows that antiphospholipid antibodies are relatively frequent in cirrhosis and that beta-2-glycoprotein I levels are not so low as to affect lupus anticoagulant detectability.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prevalence of lupus anticoagulant in patients with cirrhosis: relationship with beta-2-glycoprotein I plasma levels. 769 32

Beta 2-glycoprotein I (beta 2-GPI) binds negatively charged substances and inhibits intrinsic blood coagulation in the presence of ellagic acid-phospholipid suspension. Beta 2-GPI is thought to be an important protein in the reaction between negatively charged phospholipids and anti-phospholipid antibodies which appear in patients with lupus anticoagulant/antiphospholipid antibody syndrome. We prepared a monoclonal antibody against beta 2-GPI purified from human plasma and obtained beta 2-GPI-depleted plasma using a monoclonal antibody-coupled column. Either partial thromboplastin time or the activation of prekallikrein induced by diluted ellagic acid-phospholipid suspension in beta 2-GPI-depleted plasma was not different from that in control plasma. Beta 2-GPI inhibited the intrinsic blood coagulation only when added to control or beta 2-GPI-depleted plasma in excess (more than physiological concentrations). The intrinsic fibrinolysis in beta 2-GPI-depleted plasma induced by dextran sulfate was not impaired and, again, beta 2-GPI inhibited the intrinsic fibrinolysis only when added to control or beta 2-GPI-depleted plasma in excess. These results indicate that both in vitro Actin-induced intrinsic coagulation and dextran sulfate-induced fibrinolytic activities are significantly inhibited by more than physiological concentrations of beta 2-GPI.
 ...
PMID:Ellagic acid/phospholipid-induced coagulation and dextran sulfate-induced fibrinolytic activities in beta 2-glycoprotein I-depleted plasma. 786 69

From one patient with systemic lupus erythematosus retaining lupus anticoagulant (LAC), we established 6 Epstein-Barr virus-transformed human B cell clones secreting antibodies that affect the coagulation assay. Two and 4 of the clones secreted IgM and IgG antibodies, respectively. Although all 6 antibodies displayed anticardiolipin activity in ELISA, the increased binding activity in the presence of beta 2-glycoprotein I was limited only to the IgG antibodies. Five antibodies (two IgM and three IgG) had LAC activity which prolonged the activated partial thromboplastin time (APTT), whereas one IgG antibody shortened the APTT. Two of the IgG producing clones had an identical Ig heavy chain gene rearrangement despite their opposite effects on the coagulation assay. These results demonstrated the heterogeneity of LACs and diversity among their physiological functions.
 ...
PMID:Heterogeneity and diversity of IgM and IgG lupus anticoagulants in an individual with systemic lupus erythematosus. 794 29

Recent evidence suggests that lupus anticoagulants are immunologically distinct from the anticardiolipin antibodies. Nevertheless, the associated clinical complications exhibited by the two groups of antibodies are similar. They have been shown to have a strong association with a history of arterial and venous thrombosis, thrombocytopenia and neurological disease in patients with SLE or lupus-like disorders. The association between antiphospholipid antibodies and recurrent fetal loss is suggested by the currently available data but is not firmly established. Patients with lupus and antiphospholipid antibodies and an established history of recurrent fetal wastage are at high risk for experiencing subsequent fetal loss, but it is not yet known whether the same is true for patients without a history of fetal loss. The association of thrombosis, neurological disease, thrombocytopenia, and fetal loss in patients with non-SLE disorders has not been as extensively studied. Only recently have investigators such as Ginsberg and colleagues begun to show in prospective studies that there may, in fact, be a statistically significant risk of thrombotic events in otherwise healthy individuals with antiphospholipid antibodies. Many of the diverse minor manifestations reported in individual patients, case series, or cross-sectional studies such as livedo reticularis, leg ulcers, and hemolytic anemia may, alternatively, be due to coincidence or chance. Efforts to elucidate the mechanisms of thrombosis in patients with antiphospholipid antibodies is an area of active research. Most efforts have been based on the effects of these antibodies on endothelial cell and platelet function as well as on the fibrinolytic system. In addition, it has recently been shown that binding of antiphospholipid antibodies to phospholipids requires the serum "co-factor" beta 2-glycoprotein I. In patients with SLE selected for the presence of the lupus anticoagulant, thrombosis, or fetal loss, Viard and associates found that 17 of 47 (36%) patients had anti-beta 2-glycoprotein I antibodies. They were able to show, in their small retrospective study, that there was an association between the presence of these antibodies and anticardiolipin activity, lupus anticoagulant activity, and thrombotic events, but not with spontaneous abortion. Of patients with SLE and thrombosis (9 of 47) eight of nine were positive for anti-beta 2-glycoprotein I antibodies, seven of nine were positive for anticardiolipin antibodies, and eight of nine were positive for the lupus anticoagulant. The known inhibitory effect of beta 2-glycoprotein I on platelet aggregation, on platelet prothrombinase activity, and on the intrinsic pathway of coagulation supports the hypothesis that implicates beta 2-glycoprotein I in the pathogenesis of unwanted thrombotic events.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Clinical syndromes associated with lupus anticoagulants. 805 30

Lupus anticoagulants are antibodies that inhibit phospholipid dependent coagulation reactions in vitro. These antibodies are of clinical interest because of their association with a variety of clinical manifestations characterized by microvascular thrombosis. Although these antibodies were originally thought to be directed at negatively charged phospholipid, recent studies have suggested that they may be directed at phospholipid-protein complexes. The effect of antibodies directed against beta 2-glycoprotein I (beta 2-GP I, apolipoprotein H) on phospholipid-dependent coagulation reactions has been studied. Polyclonal and monoclonal antibodies to beta 2-GP I were found to inhibit thrombin generation in a dose dependent manner. Inhibition of thrombin formation was due to specific interaction with beta 2-GP I. There was no evidence that inhibition was due to crossreactivity with other proteins involved in the prothrombinase complex. These findings document that antibodies directed against beta 2-GP I can have anticoagulant activity analogous to lupus anticoagulant activity and are consistent with the recent observation of such activity in lupus anticoagulant patient samples.
 ...
PMID:Antibodies to beta 2-glycoprotein I inhibit phospholipid dependent coagulation reactions. 811 86


1 2 3 4 Next >>