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)

Beta 2-glycoprotein I plays a pivotal role in the binding of antiphospholipid antibodies to phospholipid in patients with antiphospholipid syndrome. In this study the nature of the epitopes on beta 2-glycoprotein I (beta2-GPI) recognised by sera from antiphospholipid syndrome (APS) patients (n = 15) was investigated and compared to rabbit polyclonal and mouse monoclonal anti-beta2-GPI antibodies. beta2-GPI was only recognised when bound to a high affinity binding support. The antigenic epitope on beta2-GPI recognised by all APS patients was also dependent on disulphide bond integrity. Digestion of beta2-GPI with elastase rapidly destroyed the epitope(s) on beta2-GPI recognised by antibodies in 91% of APS patients. The main cleavage occurred at tryptophan316-lysine317 in the fifth domain. Digestion with staphylococcal V8 protease resulted in a 50% reduction in antibody binding in 81% of patients and the cleavage sites mainly involved the first domain of the molecule. There was considerable variability in the recognition of six different species of beta2-GPI by serum from APS patients. The epitopes on beta2-GPI bound by APS sera appear conformationally determined in all patients but are quite heterogeneous in the regions of beta2-GPI that are recognised.
Thromb Haemost 2000 Sep
PMID:Heterogeneous recognition of beta 2-glycoprotein I by antibodies from antiphospholipid syndrome patients. 1101 58

Autoreactive CD4(+) T cells to beta2-glycoprotein I (beta2GPI) that promote antiphospholipid antibody production were recently identified in patients with antiphospholipid syndrome (APS). To further examine antigen recognition profiles and T-cell helper activity in beta2GPI-reactive T cells, 14 CD4(+) T-cell clones specific to beta2GPI were generated from 3 patients with APS by repeated stimulation of peripheral blood T cells with recombinant beta2GPI. At least 4 distinct T-cell epitopes were identified, but the majority of the beta2GPI-specific T-cell clones responded to a peptide encompassing amino acid residues 276 to 290 of beta2GPI (KVSFFCKNKEKKCSY; single-letter amino acid codes) that contains the major phospholipid-binding site in the context of the DRB4*0103 allele. Ten of 12 beta2GPI-specific T-cell clones were able to stimulate autologous peripheral blood B cells to promote anti-beta2GPI antibody production in the presence of recombinant beta2GPI. T-cell helper activity was exclusively found in T-cell clones capable of producing interleukin 6 (IL-6). In vitro anti-beta2GPI antibody production induced by T-cell clones was inhibited by anti-IL-6 or anti-CD40 ligand monoclonal antibody. In addition, exogenous IL-6 augmented anti-beta2GPI antibody production in cultures of the T-cell clone lacking IL-6 expression. These results indicate that beta2GPI-specific CD4(+) T cells in patients with APS preferentially recognize the antigenic peptide containing the major phospholipid-binding site and have the capacity to stimulate B cells to produce anti-beta2GPI antibodies through IL-6 expression and CD40-CD40 ligand engagement. These findings are potentially useful for clarifying the pathogenesis of APS and for developing therapeutic strategies that suppress pathogenic antiphospholipid antibody production in these patients.
Blood 2001 Sep 15
PMID:Autoreactive CD4(+) T-cell clones to beta2-glycoprotein I in patients with antiphospholipid syndrome: preferential recognition of the major phospholipid-binding site. 1153 26

Anti-prothrombin antibodies (anti-prothrombin) and anti-beta2-glycoprotein I antibodies (anti-beta2-GP I) are the most common and characterized anti-phospholipid antibodies (aPL) detected using specific enzyme-linked immunosorbent assay (ELISA) systems. Recently, lupus anti-coagulant (LA) activity detected by a phospholipid-dependent coagulation assay was reported to be associated with anti-prothrombin and/or anti-beta2-GP I. Here we show that the co-existence of IgG anti-prothrombin and LA activity might be an essential risk factor for venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE). We examined not only the levels of antibodies to prothrombin and anti-beta2-GP I (both IgG and IgM isotypes) using an ELISA system, but also LA activity detected using both diluted Russell's viper venom time (dRVVT) and STACLOT LA test in 124 patients with SLE. The SLE patients were divided into four groups according to the results of ELISA and LA assay results for each aPL: group A, ELISA+ and LA+ group B, ELISA+ and LA-; group C, ELISA- and LA+ group D, ELISA- and LA-. Regarding IgG anti-prothrombin, the prevalence of VTE was significantly higher in group A (16/35 cases, 45.7%, P < 0.001, Fisher's exact probability test) than in the other groups (B, 2/30, 6.7%; C, 1/22, 4.5%; D, 1/37, 2.7%). With respect to IgM anti-prothrombin and IgG or IgM anti-beta2-GP I, the prevalence of VTE was higher in both groups A and C than in group D, but no statistical difference in prevalence was found between groups A and C. Multivariate logistic regression analysis of risk factors for VTE confirmed that the co-existence of IgG anti-prothrombin and LA activity was the only significant risk factor for VTE (odds ratio, 19.13; 95% confidence intervals, 4.74-77.18).
Br J Haematol 2001 Sep
PMID:Anti-prothrombin antibodies combined with lupus anti-coagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus. 1155 93

Apolipoprotein H (apo H), also known as beta2-glycoprotein 1, has recently become of interest in the field of haemostasis. As apo H is elevated in diabetes mellitus and dyslipidaemia, we wished to test the hypothesis that serum apo H concentration was related to fasting plasma glucose and insulin as well as blood pressure, body mass index, hip/waist ratio and serum lipids in normal individuals. Eighty-one healthy young individuals (46 females and 35 males) were studied. Their age was 20.7 +/- 0.75 years. Serum apo H significantly correlated with fasting plasma glucose (r = 0.24, P = 0.03) and serum LDL cholesterol (r = 0.30, P = 0.006). In the females serum apo H significantly correlated with serum cholesterol concentration (r = 0.30, P = 0.04) and in males with serum HDL cholesterol concentration (r = 0.35, P = 0.04). In multifactorial regression analysis for serum apo H and the other variables for the 81 subjects, only gender and fasting plasma glucose remained statistically significant in the model. Serum apo H concentrations would be expected to increase by 21.7 mg/L for each single mmol/L increase in fasting plasma glucose (95% CI 2.3-41 2), P = 0.029, and to increase by 17.0 mg/L if the gender is male (95% Cl 0.7-332), P= 0.041.
Ann Clin Biochem 2001 Sep
PMID:Serum apolipoprotein H and its relationship to blood pressure, serum lipids, fasting plasma glucose and insulin in normal individuals. 1158 27

The antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis, recurrent pregnancy loss, and thrombocytopenia combined with laboratory tests that indicate the presence of antibodies against phospholipid-binding proteins. The antibodies are directed against a complex of phospholipid with a protein such as beta 2-glycoprotein I (beta 2-GPI) or prothrombin and are detected by means of phospholipid-dependent coagulation assays (known as assays for lupus anticoagulants) and by ELISAs that contain beta 2-GPI and a phospholipid (e.g., cardiolipin). The antiphospholipid syndrome can be associated with other connective tissue disorders such as systemic lupus erythematosus or may be the only manifestation of an autoimmune disorder. Management of patients with this disorder usually includes anticoagulation, which has been found to reduce the rate of recurrence of venous and arterial thrombosis as well as the rate of fetal loss.
J Thromb Thrombolysis 2001 Sep
PMID:Diagnosis and management of patients with the antiphospholipid syndrome. 1171 94

A case of antiphospholipid syndrome (APS) is reported. A 48-year-old man visited our hospital because of proteinuria. He had suffered from thrombosis and had high titers of antibodies to beta2-glycoprotein I (abeta2GPI) and anticardiolipin antibodies (aCLIgG) and thrombocytopenia. We started anticoagulation therapy using warfarin combined with prednisolone. Although platelet count was improved, the titers of anti-beta2GPI and aCLIgG still remained high. Therefore, double-filtration plasmapheresis (DFPP) was carried out to remove the antibodies. After the treatment with DFPP, cyclophosphamide was administered. These therapies resulted in lower titers of abeta2GPI and aCLIgG and no more thrombosis occurred. A combination therapy using warfarin, prednisolone, cyclophosphamide and DFPP might be effective for the treatment of patients with APS.
Intern Med 2002 Sep
PMID:Antiphospholipid syndrome treated with prednisolone, cyclophosphamide and double-filtration plasmapheresis. 1232 1

Three antiphospholipid antibodies (aPLs), namely, antiphosphatidylinositol antibody (antiinositol antibody), antiphosphatidylserine antibody (antiserine antibody), and anticardiolipin. beta 2-glycoprotein I complex antibody (antiCL. beta 2-GPI antibody), were determined in 49 children with idiopathic thrombocytopenic purpura (ITP) consisting of 14 newly-diagnosed cases and 35 chronic cases. Determination of aPL was performed twice in the newly-diagnosed patients, once each during the acute and convalescent phases, and once in the chronic patients. The positive rates in the acute and convalescent phases of the newly-diagnosed group and in the chronic group were, respectively, 14.3%, 28.6%, and 18.8% for the antiinositol antibody, 14.3%, 14.3%, and 15.6% for the antiserine antibody, and 21.4%, 28.6%, and 25.0% for either of these 2 antibodies. Thus, antiinositol and antiserine aPLs were present at high incidences; however, all patients were negative for the antiCL. beta 2-GPI antibody. No correlation was noted between either the antiinositol or the antiserine antibody and peripheral platelet count, anti-GP IIb/IIIa antibody or PAIgG. Thus, although some aPLs are present in both acute and chronic pediatric ITP, the aPLs seems to be of an infectious disease type. No results that suggest possible involvement of aPLs in ITP pathology were obtained.
Rinsho Ketsueki 2002 Sep
PMID:[Antiphospholipid antibodies in children with idiopathic thrombocytopenic purpura]. 1241 85

Patients with prolonged clotting times caused by lupus anticoagulant (LAC) are at risk for thrombosis. This paradoxal association is not understood. LAC is frequently caused by anti-beta2-glycoprotein I (beta 2GPI) antibodies. Antibody-induced dimerization of beta 2GPI increases the affinity of beta 2GPI for phospholipids, explaining the observed prolonged clotting times. We constructed dimers of beta 2GPI that mimic effects of beta 2GPI-anti-beta 2GPI antibody complexes, and we studied their effects on platelet adhesion and thrombus formation in a flow system. Dimeric beta 2GPI increased platelet adhesion to collagen by 150% and increased the number of large aggregates. We also observed increased platelet adhesion to collagen when whole blood was spiked with patient-derived polyclonal anti-beta 2GPI or some, but not all, monoclonal anti-beta 2GPI antibodies with LAC activity. These effects could be abrogated by inhibition of thromboxane synthesis. A LAC-positive monoclonal anti-beta 2GPI antibody, which did not affect platelet adhesion, prevented the induced increase in platelet adhesion by beta 2GPI dimers. Furthermore, increased platelet adhesion disappeared after preincubation with receptor-associated protein, a universal inhibitor of interaction of ligands with members of the low density lipoprotein receptor family. Using co-immunoprecipitation, it was shown that dimeric beta 2GPI can interact with apolipoprotein E receptor 2 (apoER2'), a member of the low density lipoprotein receptor family present on platelets. These results demonstrate that dimeric beta 2GPI induces increased platelet adhesion and thrombus formation, which depends on activation via apoER2'.
J Biol Chem 2003 Sep 05
PMID:Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'. 1280 92

Hybridomas expressing murine gammadelta T-cell receptors were found to produce cytokines in response to cardiolipin (CL) and structurally related anionic phospholipids. This response required serum at concentrations related to the amount of CL in cultures. The purified serum factor, beta2-glycoprotein 1 (beta2-GP1) (apolipoprotein H), supported the CL response alone, whereas several other serum proteins and ovalbumin did not. beta2-GP1 is known to form complexes with anionic phospholipids, particularly CL, which are often recognized by pathological autoantibodies. We speculate that gammadelta T cells also recognize such complexes and that the hybridoma response reported here reflects this specificity.
Scand J Immunol 2003 Sep
PMID:Hybridomas expressing gammadelta T-cell receptors respond to cardiolipin and beta2-glycoprotein 1 (apolipoprotein H). 1295 Jun 85

The aim of this study was to compare the prevalence of anticardiolipin antibodies with other types of antiphospholipid antibodies (aPL) (antiphosphatidylserine--aPS, antiphosphatidylinositol--aPI, antiphosphatidylethanolamine--aPE) in patients with lupus nephritis and to find if the examination of a panel of various aPL is valuable for further diagnosis of patients. Additionally we determined the levels of autoantibodies against beta2-glycoprotein I (beta2GPI) and oxidized low-density lipoprotein (anti-oxLDL) and also investigated the relationship between antibodies against beta2GPI and oxLDL, which were assessed by ELISA methods. Twenty-two patients with lupus nephritis were studied. The control group consisted of 62 healthy blood donors. A statistically significant higher occurrence of all aPLs in the patients with lupus nephritis in comparison to the control group was found. The prevalence of polyspecific antibodies, which reacted with at least two various phospholipids, was 82% in the group of SLE patients. Significantly higher levels of IgG anti-beta2GPI in the sera of SLE patients (p = 0.0003) was detected. The levels of anti-oxLDL in the sera of the patients group did not differ significantly from the control one. Some positive samples for anti-beta2GPI and negative for aCL or anti-oxLDL and vice versa were found. It ca be concluded that the production of aPL including anti-beta2GPI and anti-oxLDL in the lupus nephritis patients is higher in comparison with healthy blood donors. We assume that the estimation of various types of aPL may be important in the selection of the group patients with renal diseases. The synthesis of aPL can reflect the spreading of the autoimmune response for several antigens modified on the vessel wall.
Ren Fail 2003 Sep
PMID:Antiphospholipid antibodies in patients with lupus nephritis. 1457 83


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