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)

To characterize the reactivity pattern of Abs directed to beta2-glycoprotein I (anti-beta2GPI) in patients with anti-phospholipid syndrome, we have purified anti-beta2GPI Abs by affinity chromatography using the IgG fractions from sera of five different anti-phospholipid syndrome patients. Affinity-purified anti-beta2GPI were shown to be representative of Abs found in human sera because their activity could be virtually abolished from the IgG preparations after repeated absorptions on immobilized human beta2GPI column. Our results show that affinity-purified anti-beta2GPI: 1) do react with beta2GPI in the absence of any phospholipid, as demonstrated by the lack of phosphorus contaminant in the employed reagents, as well as by their comparable binding activity before and after extensive delipidation procedure; 2) can recognize beta2GPI regardless of its origin from different animal species; 3) are able to bind soluble beta2GPI with a mean Kd value of 4.65 x 10(-6) M (range 3, 4-7, 2 x 10(-6) M); 4) significantly enhance their binding avidity when beta2GPI is linked to a solid support; and 5) appear to be mainly monoreactive autoantibodies. In conclusion, we have shown that human polyclonal anti-beta2GPI are low affinity, mainly monoreactive autoantibodies directed to an epitope located on native beta2GPI, preserved along the species evolution.
J Immunol 1996 Dec 15
PMID:The anti-beta2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species' evolution. 895 27

Antiphospholipid antibodies (aPL) characterize patients at risk for both arterial and venous thrombotic complications. Recently it has been recognized that the presence of plasma proteins such as beta 2-glycoprotein I(beta 2 GPI) and prothrombin are essential for the binding of aPL to phospholipids and that these proteins are probably the real target of aPL. The discovery of these new antigens for aPL introduces the possibility of new assays to detect the presence of aPL. However, it is not known whether these assays improve the identification of patients at risk for thrombosis. In this retrospective study we compared the value of the classic assays LAC (lupus anticoagulant) and ACA (anticardiolipin antibodies) to detect aPL associated with thrombotic complications, with new assays which are based on the binding of aPL to the plasma proteins prothrombin and beta 2GPI. To do so, we have used these assays in a group of 175 SLE patients and correlated the positivity of the different assays with the presence of a history of venous and arterial thrombosis. Control groups were patients without SLE but with LAC and/or ACA and thrombosis (n = 23), patients with thrombosis without LAC and ACA (n = 40) and 42 healthy controls. In the univariate analysis, in which no distinction has been made between high and low antibody levels, we confirmed LAC and ACA to be related to both arterial and venous thrombosis. Anti-beta 2GPI- and anti-prothrombin-antibodies, both IgG and IgM correlate with venous thrombosis and anti-beta 2GPI-IgM with arterial thrombosis. Multivariate analysis showed that LAC is the strongest risk factor (OR 9.77; 95% CI 1.74-31.15) for arterial thrombosis. None of the other factors is a significant additional risk factor. For venous thrombosis LAC is the strongest risk factor (OR 6.55; 95% CI 2.36-18.17), but ACA-IgM above 20 MPL units also appeared to be a significant (p = 0.0159) risk factor (OR 3.90; 95% CI 1.29-11.80). Furthermore, the presence of anti-beta 2GPI- and/or anti-prothrombin-antibodies in LAC positive patients (n = 60) does not increase the risk for thrombosis. The results showed that (i) the LAC assay correlates best with a history of both arterial and venous thrombosis and (ii) neither the anti-beta 2GPI ELISA nor the anti-prothrombin ELISA gives additional information for a thrombotic risk in SLE patients.
Thromb Haemost 1996 Dec
PMID:Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies. 926 10

The clinical significance of anti-beta 2 glycoprotein I (beta 2-GPI) antibodies was evaluated in patients with antiphospholipid syndrome (APS), primary and secondary to systemic lupus erythematosus (SLE). Anti-beta 2-GPI were tested in 120 patients (39 primary APS, 32 APS with SLE and 49 SLE without APS) by ELISA utilizing irradiated plates in the absence of cardiolipin. Anticardiolipin antibodies (aCL) and antiphosphatidylserine antibodies were also measured in the same patients using standardized assays. Anti-beta 2-GPI titres correlated strongly to those of aCL (r = 0.816, P = 0.0001), and to those of antiphosphatidylserine antibodies (r = 0.841, P = 0.0001). Anti-beta 2-GPI were detected in 53.5% of APS patients (38/71), but only in 4.1% of SLE patients without APS (2/49). In the latter group, 24.5% (12/49) of patients had a positive titre of aCL. The anti-beta 2-GPI assay showed higher specificity for APS than the aCL in APS (96 vs 75%, respectively, chi 2 = 6.75, P = 0.00094). Our findings suggest that the assay of anti-beta 2-GPI may improve the specificity for APS.
Br J Rheumatol 1996 Dec
PMID:Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome. 940 76

A 33-year-old man presented malar rash in April, 1992. The rash had gradually developed and he was admitted to our hospital in February, 1994. Laboratory findings showed proteinuria of 0.5-0.8 g/ day, thrombocytopenia (4.8 x 10(4)/mm3), false positive serologic test for syphilis, anti-nuclear antibody with a speckled type at a titer of 1 : 80. Activated partial thromboplastin time was prolonged (41.3 s), and anti-beta 2-GPI antibody was strongly positive (56.6 U/ml on enzyme linked immunosorbent assay). The diagnosis of systemic lupus erythematosus with antiphospholipid syndrome was made and prednisolone 60 mg/day improved his manifestations. He could be discharged in July, 1994. Nine months after the discharge he developed dyspnea, and he was admitted to our hospital again. On admission the blood pressure was 212/170 mmHg, Levine III/VI systolic murmur was noted at the apex of heart. Significant laboratory findings showed as follows: WBC 15, 110/mm3 (Neu 73%, Lym 18%), RBC 380 x 10(4)/mm3, Hb 10.2 g/dl, Plt 20.0 x 10(4)/mm3, GOT 23 IU/l, GPT 21.
Ryumachi 1996 Dec
PMID:[Acute cardiac failure due to dilated cardiomyopathy in systemic lupus erythematosus with antiphospholipid antibody]. 912 25

The function of beta2-glycoprotein I (beta2GPI), a 50-kDa serum glycoprotein, is not completely understood but has been suggested to be involved in the regulation of thrombosis (Brighton, T. A., Hogg, P. J., Dai, Y.-P., Murray, B. H., Choing, B. H., and Chesterman, C. N. (1996) Br. J. Haematol. 93, 185-194) and the clearance of phosphatidylserine (PS)-expressing cells (Chonn, A., Semple S. C., and Cullis P. R. (1995) J. Biol. Chem. 270, 25845-25849). To further understand the role of this protein, we characterized the ability of beta2GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. beta2GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. beta2GPI also inhibited the procoagulant activity of PS liposomes. In vitro phagocytosis studies showed 20-fold greater uptake of PS liposomes over phosphatidylcholine liposomes. This enhanced uptake was maintained even after PS was "shielded" with beta2GPI and further increased upon the addition of beta2GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bound beta2GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of beta2GPI and further increased upon the addition of beta2GPI antibodies. It is concluded that beta2GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.
J Biol Chem 1997 Dec 05
PMID:Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition. 938 64

beta 2-Glycoprotein I (beta 2-GPI), a plasma protein with in vitro anticoagulant properties, has been recognized to have an important role in the antiphospholipid syndrome (APS) as a cofactor and an (co)antigen in ELISA assays. Although beta 2-GPI levels were found to be increased in some patients with APS, the clinical value of measuring beta 2-GPI levels in APS is not known. Several reports have suggested that anti-beta 2-GPI antibodies may be a marker for the APS and might be more specific for the vascular complications of the APS than anticardiolipin antibodies. There have been major discoveries about phospholipid (PL) and antibody binding sites on beta 2-GPI, although more studies are needed. Reports of changes in cell membrane PL composition or exposure of other anionic molecules by apoptosis, cell activation and oxidative injury suggest mechanisms to explain beta 2-GPI binding and the generation of cryptic epitopes for aPL/anti-beta 2-GPI antibodies.
Br J Rheumatol 1997 Dec
PMID:beta 2-Glycoprotein I and anti-beta 2-glycoprotein I antibodies: where are we now? 944 84

We studied the structure of N-linked carbohydrates bound to apolipoprotein H by a combination of two methods which make use of lectins. Digoxigenin-labelled lectins are used for the structural characterization of carbohydrate chains of glycoproteins. Concanavalin A lectin affinity chromatography was used to analyse apolipoprotein H according to the characteristics of its carbohydrate chain inner to sialic acid residues. Our results from digoxigenin-labelled lectins analysis showed that apolipoprotein H gave positive bands to SNA, DSA, GNA, PNA and AAA lectins. Apolipoprotein H gave a negative band when reacted with MAA lectin. When we applied apolipoprotein H onto the Concanavalin A lectin column no detectable amounts of protein were eluted with Concanavalin A buffer. After adding a buffer with low sugar concentration (10 mM glucoside) a large amount of apolipoprotein H was recovered. These molecules of apolipoprotein H weakly bound to the lectin. When a higher sugar concentration (500 mM mannoside) was added most of the sample applied was eluted. These molecules of apolipoprotein H firmly bound to the column having high affinity for the lectin. These results combined with those coming from the digoxigen-labeled lectins method enable us to understand the inner structure of carbohydrate chains with their outer branches. Molecules of apolipoprotein H which weakly bind to Concanavalin A could bear complex N-glycans organized in biantennary or truncated hybrid structures. Firmly bound apolipoprotein H referred to molecules rich in N-glycan hybrid structures. They have an outer branch belonging to the high mannose carbohydrate chains which explain the ability to bind to the column and an other main branch bearing the sequence galactose beta-(1-4)-N-acetylglucosamine beta-(1-2) mannose. Galactose could be the terminal sugar or, alternatively, be masked with sialic acid alpha-(2-6) terminally linked.
J Lipid Mediat Cell Signal 1997 Dec
PMID:Characterization and representative structures of N-oligosaccharides bound to apolipoprotein H. 952 27

We have previously demonstrated that lupus anticoagulant antibodies from patients with systemic lupus erythematosus (SLE) specifically recognize hexagonal (II) phase phosphatidylethanolamine (PE), but not bilayer PE (Thromb Haemost 1989; 62: 892). In those studies, the involvement of proteins in this recognition was not evaluated. To address this issue, we have isolated IgG lupus anticoagulant antibodies from the plasma of SLE patients and evaluated the inhibition of lupus anticoagulant activity by hexagonal (II) phase PE in the presence and absence of purified plasma proteins. All six of the IgG lupus anticoagulant antibodies tested were inhibited by hexagonal (II) phase PE in the presence, but not the absence, of human prothrombin. In contrast, little or no inhibition was observed with prothrombin alone or with PE in combination with either beta2-glycoprotein I or annexin V. These data indicate that, for certain lupus anticoagulant antibodies, inhibition by hexagonal (II) phase PE is dependent on prothrombin, suggesting that these antibodies recognize a complex of PE and prothrombin.
Thromb Haemost 1998 Dec
PMID:Inhibition of lupus anticoagulant activity by hexagonal phase phosphatidylethanolamine in the presence of prothrombin. 986 64

This study was undertaken to investigate the influence of beta 2-glycoprotein I (GPI) on anticardiolipin antibody (aCL) titration in leprosy. The study group consisted of 140 sera from patients with multibacillary leprosy (46 borderline, 94 lepromatous). The group included newly diagnosed, previously untreated patients, patients under treatment and patients released from treatment. GPI addition enhanced significantly the aCL titres in sera from lepromatous leprosy but not in those from borderline leprosy. Moreover, when the patients were classified according to their bacteriological status, aCL titres were found to be significantly higher in skin smear positive patients compared to bacteriologically negative patients. Thus, the present study demonstrates that aCL in multibacillary leprosy patients are mainly of the GPI-dependent type and emphasizes the importance of GPI addition for aCL titration in leprosy.
Lepr Rev 1998 Dec
PMID:beta 2-Glycoprotein I-dependence of anticardiolipin antibodies in multibacillary leprosy patients. 992 10

Prothrombin time (PT) is routinely used to monitor oral anticoagulant treatment in patients with the antiphospholipid antibody syndrome (APS). The fact that PT is a phospholipid (PL)-dependent coagulation test raises the possibility that lupus anticoagulant (LA) might interfere with this test, thus complicating the control of anticoagulant treatment. The effect of 6 affinity-purified preparations of anti- (a)beta2-glycoprotein I (GPI) antibodies with LA activity on the PT was tested. Instead of prolonging PT as expected, the abeta2-GPI antibodies reduced the PT of both normal plasma and anticoagulated plasma by a mean of 2.4 seconds and 5.6 seconds, respectively. This effect was also observed using other 5 commercially available preparations of thromboplastin. The abeta2-GPI-mediated reduction in PT was dose-dependent and was lost upon removal of beta2-GPI. The failure of abeta2-GPI antibodies to express LA activity in PT was found to depend on the fact that calcium ions were added together with PL at the beginning of the assay. In fact, modification of the standard diluted Russell viper venom time (dRVVT) test by adding calcium ions together with PL resulted in a loss of abeta2-GPI anticoagulant activity. The procoagulant effect was not as evident in an assay that used stimulated monocytes as a source of thromboplastin. These results show that abeta2-GPI antibodies exhibit an 'in vitro' procoagulant effect in PT and an anticoagulant effect in dRVVT only when the interaction with their antigen and PL occurs in the absence of calcium ions.
Blood 1999 Dec 01
PMID:Procoagulant effect of anti-beta2-glycoprotein I antibodies with lupus anticoagulant activity. 1057 96


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