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 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.
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PMID:Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome. 940 76

Apolipoprotein H (apoH), also known as beta 2-glycoprotein-I, is considered to be a cofactor for the binding of certain antiphospholipid autoantibodies to negatively charged phospholipids. Genetically determined structural abnormalities in the lipid binding domain(s) of apoH can affect its ability to bind lipid and consequently the production of the autoantibodies. In this study we have identified two common structural mutations at codons 316 and 306 in the fifth domain of apoH which rendered apoH unable to bind to negatively charged phosphatidylserine (PS). The missense mutation at codon 316 (TGG --> TCG) replaces Trp316 with Ser316 and disrupts the integrity of four highly conserved hydrophobic amino acids sequence at positions 313-316, which is a potential protein-lipid hydrophobic interaction site. The missense mutation at codon 306 (TGC --> GGC) involves the substitution of Cys306 by Gly306 which causes the disruption of a disulfide bond between Cys281 and Cys306 and affects the normal configuration of the fifth domain of apoH that appears to be critical for clustering positively charged amino acids along with four hydrophobic amino acids sequence. ApoH from the two homozygotes (Ser316/Ser316) and all seven compound heterozygotes (Ser316/Gly306) failed to bind to PS; all heterozygotes at one or the other sites and wild type showed normal PS binding. These data indicate that the fifth domain of apoH harbors the lipid binding region. An estimated 2 million Caucasians in the United States, who are compound heterozygotes for the two mutations, may be precluded from producing apoH-dependent antiphospholipid autoantibodies.
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PMID:Identification of structural mutations in the fifth domain of apolipoprotein H (beta 2-glycoprotein I) which affect phospholipid binding. 906 52

Lipoprotein(a) [Lp(a)], which has been shown to interact with fibrin(ogen) and other components of the blood clotting cascade, is a major independent risk factor for atherothrombotic disease in humans. The physiological function(s) of Lp(a), as well as the precise mechanism(s) by which high plasma levels of Lp(a) increase risk are unknown. Identification of further potential apo(a)-protein ligands may be crucial to illuminate apo(a)'s function(s) and pathophysiological properties. We used the repetitive apo(a) kringle IV type 2, which is variable in number in apo(a), to screen a human liver cDNA library by the yeast two-hybrid interaction trap system. Among 11 positive clones that emerged from the screen, eight clones were identified as beta-2 glycoprotein I and one as fibronectin. Coimmunoprecipitation experiments confirmed that beta-2 glycoprotein I and apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1 cells, which ectopically expressed apo(a). The apo(a)-beta2-glycoprotein I interaction indicates new potential roles for Lp(a) in fibrinolysis and autoimmunity.
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PMID:Novel interaction of apolipoprotein(a) with beta-2 glycoprotein I mediated by the kringle IV domain. 926 65

Male (NZW x BXSB)F1 (W/BF1) mice develop a systemic lupus-like syndrome characterized by thrombocytopenia, coronary vascular disease, nephritis, and anticardiolipin antibodies. Three stable hybridoma cell lines secreting monoclonal anticardiolipin antibodies were developed from these mice by fusing their splenic lymphocytes with nonsecreting myeloma cell line, NS-1. Monoclonal antibody A1.17 reacted with cardiolipin in a beta2-Glycoprotein I-dependent manner. The epitope for this antibody consisted of beta2-glycoprotein I bound to cardiolipin or immobilized on plastic plates. Other anionic phospholipid-binding proteins, such as prothrombin or annexin V, had no significant effect in the reactivity of these antibodies. The specificity is similar to the autoimmune anticardiolipin antibodies described in patients with systemic lupus erythematosus and other infectious diseases. In contrast, monoclonal antibodies A1.72 and A1.84 reacted with cardiolipin in the absence of beta2-glycoprotein I. Beta2-glycoprotein I, either in the fluid phase or bound to cardiolipin, inhibited the binding of these antibodies. The specificity of the latter two antibodies was similar to that described in patients with syphilis and allied disorders. Both types of antibodies had lupus anticoagulant properties. Thus lupus-prone male (NZW x BXSB)F1 (W/BF1) mice develop both beta2-glycoprotein I-dependent and beta2-glycoprotein I-independent anticardiolipin antibodies.
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PMID:Characterization of beta2-glycoprotein I-dependent and -independent "antiphospholipid" antibodies from lupus-prone NZW/BXSB F1 hybrid male mice. 932 49

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.
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PMID:Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition. 938 64

Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid syndrome (APS) were found by many investigators, but their results appeared contraversional. We studied clinical significance of antibodies to beta 2-glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL) and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI, respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS development as a whole, its separate clinical symptoms (venous and arterial thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more frequently in the sera positive by LA and aCL. It is interesting that we discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is clinically important for upgrading diagnosis of APS.
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PMID:[Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new laboratory marker of antiphospholipid syndrome]. 957 46

Screening of serum by using a surface plasmon resonance analysis assay identified beta2-glycoprotein-I/apolipoprotein H as a plasma component binding to the renal epithelial endocytic receptor megalin. A calcium-dependent megalin-mediated beta2-glycoprotein-I endocytosis was subsequently demonstrated by ligand blotting of rabbit renal cortex and uptake analysis in megalin-expressing cells. Immunohistochemical and immunoelectron microscopic examination of kidneys and the presence of high concentrations of beta2-glycoprotein-I in urine of mice with disrupted megalin gene established that megalin is the renal clearance receptor for beta2-glycoprotein-I. A significant increase in functional affinity for purified megalin was observed when beta2-glycoprotein-I was bound to the acidic phospholipids, phosphatidylserine and cardiolipin. The binding of beta2-glycoprotein-I and beta2-glycoprotein-I- phospholipid complexes to megalin was completely blocked by receptor-associated protein. In conclusion, we have demonstrated a novel receptor recognition feature of beta2-glycoprotein-I. In addition to explaining the high urinary excretion of beta2-glycoprotein-I in patients with renal tubule failure, the data provide molecular evidence for the suggested function of beta2-glycoprotein-I as a linking molecule mediating cellular recognition of phosphatidylserine-exposing particles.
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PMID:beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin. 972 58

The binding and uptake of phosphatidylserine (PS)-expressing cells appears to involve multiple receptor-mediated systems that recognize the lipid either directly or indirectly through intermediate proteins that form a molecular bridge between the cells. Here we show that beta2-glycoprotein I (beta2GPI), a 50-kDa serum glycoprotein, binds PS-containing vesicles and serves as an intermediate for the interaction of these vesicles with macrophages. Chemical modification of lysines and cysteines abolished beta2GPI-dependent PS uptake by inhibiting the binding of PS to beta2GPI and the binding of PS.beta2GPI complex to macrophages, respectively. Recognition was mediated by beta2GPI and not by the lipid because antibodies to beta2GPI inhibited binding of the complex to macrophages. These results indicate that human (THP-1-derived) macrophages bind beta2GPI only after it is bound to its lipid ligand. Competition experiments with monosaccharides that inhibit lectin-dependent interactions, and PS.beta2GPI binding experiments using deglycosylated beta2GPI, suggested that carbohydrate residues were not required for macrophage recognition of the complex. Antibodies to putative macrophage PS receptors (CD36, CD68, and CD14) did not inhibit uptake of the complex. These data suggest that beta2GPI can bind cells that fail to maintain membrane lipid asymmetry and generate a specific bridging moiety that is recognized for clearance by a phagocyte receptor that is distinct from CD36, CD68, and CD14.
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PMID:Characterization of phosphatidylserine-dependent beta2-glycoprotein I macrophage interactions. Implications for apoptotic cell clearance by phagocytes. 978 40

Beta-2-glycoprotein I (beta2GPI), a 50-kDA serum glycoprotein that binds negatively charged phospholipids plays a role in coagulation, thrombosis, and the clearance of phosphatidylserine expressing cells. Because of its recently recognized role in several autoimmune responses, we have developed a method that quantifies plasma beta2GPI levels by using a competitive ELISA assay. When combined with data from a standard ELISA, this method determines the concentration of free beta2GPI and the fraction of antibody-bound beta2GPI thereby facilitating quantification of total antigen in individuals with autoimmune antibodies. Standard competitive inhibition ELISA was compared with this method, which uses known amounts of standard beta2GPI added to the plasma as an internal standard. Identical results were obtained with both methods for plasma samples from normal individuals that did not contain blocking antibodies. Analysis of plasma from antiphospholipid syndrome patients (patients with autoantibodies to beta2GPI) by the internal standard method, however, resulted in significantly lower apparent beta2GPI levels indicating that a substantial fraction of the plasma beta2GPI was bound by antibody.
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PMID:Estimation of plasma beta-2-glycoprotein levels by competitive ELISA. 979 17

Thrombosis in the antiphospholipid syndrome has been associated with acquired deficiency of the anticoagulant protein S. We sought evidence that beta2-glycoprotein I, a major target antigen for antiphospholipid antibodies, is involved in regulation of protein S activity. Incubation of purified protein S or plasma with beta2-glycoprotein I reversed functional modulation of protein S by its plasma inhibitor, the C4b-binding protein. In a plasma-free ELISA, beta2-glycoprotein I prevented the binding of protein S and C4b-binding protein when preincubated with immobilized protein S but not when similarly preincubated with C4b-binding protein. beta2-glycoprotein I in fluid phase interfered with precipitation of protein S by sepharose-bound C4b-binding protein. Effects of beta2-glycoprotein I on protein S function were inhibited by one of four monoclonal anti-beta2-glycoprotein 1 antibodies. These data suggest that beta2-glycoprotein I helps maintain adequate plasma levels of circulating free, active protein S. Antiphospholipid (anti-beta2-glycoprotein I) antibodies might cause sporadic thrombosis, at least in part, by impairing this novel regulatory mechanism.
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PMID:Enhancement of protein S anticoagulant function by beta2-glycoprotein I, a major target antigen of antiphospholipid antibodies: beta2-glycoprotein I interferes with binding of protein S to its plasma inhibitor, C4b-binding protein. 1036 49


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