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)

A subset of patients with systemic lupus erythematosus has autoantibodies to acidic phospholipids. Since lipids are poor immunogens, the mechanism responsible for the induction of these antibodies is unclear. Immunization of a normal rabbit and normal mice with purified human beta 2-glycoprotein I (apolipoprotein H) resulted in the production of high levels of two non-cross-reactive antibody populations, anti-apolipoprotein H, and antiphospholipid. The antiphospholipid antibodies had binding specificities indistinguishable from autoantibodies obtained from human and murine lupus. These findings suggest a novel mechanism for the induction of antiphospholipid autoantibodies.
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PMID:Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H). 152 19

A plasma protein is required as a cofactor for the binding of antiphospholipid antibodies to phospholipids. This protein has been identified as beta 2-glycoprotein I, an apolipoprotein that binds to negatively charged phospholipids and is a natural inhibitor of the coagulation cascade. It is not certain whether antiphospholipid antibodies bind to beta 2-glycoprotein I alone, to beta 2-glycoprotein I-phospholipid complex, or to a phospholipid epitope modified by beta 2-glycoprotein I. We used isolated beta 2-glycoprotein I and purified IgG and IgM antiphospholipid antibodies from serum or plasma of patients with the antiphospholipid syndrome to study the relation between antiphospholipid antibodies and beta 2-glycoprotein I in enzyme-linked immunosorbent assays. IgG antiphospholipid antibodies did not bind to beta 2-glycoprotein I when it was used as an antigen on the assay plate. The binding of IgG and IgM antiphospholipid antibodies to phospholipid was enhanced when beta 2-glycoprotein I was added to the phospholipid antigens either before or together with the antiphospholipid antibodies. The degree of enhancement varied across patients. IgM antiphospholipid antibodies required less cofactor for binding to phospholipid antigens. These results confirm the requirement of beta 2-glycoprotein I as a cofactor for the binding of autoimmune antiphospholipid antibodies to phospholipids.
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PMID:Antiphospholipid cofactor. 144 Jul 26

Autoimmune aPL are associated with a well-defined clinical syndrome of vascular thromboses, recurrent fetal loss, thrombocytopenia, livedo reticularis, and valvular and neurologic abnormalities. A clinical diagnosis of SLE need not be present, and aPL syndrome in the absence of other well-defined autoimmune disease is termed PAPS. A positive test for aPL is defined by enzyme-linked immunoassay (aCL) or by functional coagulation assay (LAC). Anticardiolipin antibody and LAC are similar but probably not identical antibodies. The false-positive test for syphilis is less closely associated with clinical complications than are aCL and LAC. The mechanism of action of aPL is not yet known, although many theories have been advanced. Recent identification of beta 2-glycoprotein I, a serum glycoprotein, as an aPL cofactor suggests that inhibition of this protein's anticoagulant activity may be important. Autoimmune aPL differ from infection-induced aPL in important antibody characteristics, including IgG subclass, light chain preference, antibody avidity, and cofactor requirement. Both recognize negatively charged phospholipids, but various physical characteristics of the phospholipids alter the recognition patterns. Treatment of the aPL syndrome is not well defined. Anticoagulation with heparin, coumadin, or aspirin are currently widely used. Although corticosteroid, immunosuppressive therapy, and plasmapheresis may be used for severe, fulminant thrombosis, the efficacy of this treatment has yet to be proved.
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PMID:Antiphospholipid antibody syndrome. 156 40

The complete primary structure of bovine beta 2-glycoprotein I was determined by a combination of cDNA and peptide sequencing. Bovine beta 2-glycoprotein I was purified from citrated plasma, and by sequencing selected peptides, the complete disulfide bridge patterns of the 11 disulfide bridges were established as well as the positions of the five asparagine-linked carbohydrate groups. Bovine beta 2-glycoprotein I comprises five mutually homologous domains or Short Consensus Repeats, each containing two disulfide bridges, except for the fifth most C-terminal domain which diverges from the Short Consensus Repeat consensus by containing an additional disulfide bridge. In the four N-terminal domains, the first and third and the second and fourth half-cystines are disulfide-linked, while in the fifth domain the first and fourth, the second and fifth, and the third and sixth half-cystines are disulfide-linked.
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PMID:Complete primary structure of bovine beta 2-glycoprotein I: localization of the disulfide bridges. 156 19

Human apolipoprotein H (APOH) is associated with lipoprotein present in plasma. It has been shown that APOH has structural similarities with the regulation of complement activation (RCA) protein superfamily and is involved in phospholipid binding interactions on platelets and as an autoantigen in complex with anionic phospholipids. Nevertheless, additional functional studies are necessary to establish the physiological role of APOH. By hybridizing a cDNA probe for APOH to a panel of somatic cell hybrids, we show that the structural locus for this protein maps to 17q23----qter and is therefore not part of the RCA cluster on chromosome 1. The site of biosynthesis for APOH was established by Northern blot analysis. Hybridization of the APOH cDNA probe to total liver RNA identified a transcript of approximately 1.5 kb.
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PMID:Assignment of apolipoprotein H (APOH: beta-2-glycoprotein I) to human chromosome 17q23----qter; determination of the major expression site. 158 54

Anticardiolipin antibodies (aCL) found in sera from patients with SLE react with cardiolipin (CL) in the presence of a 50-kDa serum cofactor. The cofactor, which was identified to be beta 2-glycoprotein I by sequencing the N-terminal amino acids, not only enhances CL binding by antibodies in SLE but also depresses it by antibodies associated with syphilis. Cofactor-dependent binding of aCL in SLE to solid phase CL was competitively inhibited by the simultaneous addition of fluid phase CL but was unaffected by either prior or simultaneous addition of a high excess of the cofactor. Binding of aCL in syphilis to solid phase CL was competitively inhibited by either addition of the cofactor or fluid phase CL. aCL in SLE reacted with CL, PS, and PA in the presence of cofactor. In contrast, biotinyl-cofactor bound directly to these anionic phospholipids (PL) and also to PG. These results show that the cofactor-CL complex bears an epitope that confers recognition specificity for aCL in SLE, in contrast with direct CL recognition by syphilitic aCL. The direct binding of the cofactor to PL suggests that the cofactor dependence of aCL binding to PL is due to recognition by aCL of a unique epitope generated upon the formation of the cofactor-CL complex.
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PMID:Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. 160 35

C-reactive protein (CRP) is thought to play an important role in immunomodulation. The exact biologic function of this pentraxin protein is, however, still unclear. Here we report experiments designed to further characterize the binding properties of CRP. Using purified human CRP it could be shown that CRP immobilized onto polystyrene surfaces or onto latex beads binds distinct plasma glycoproteins including IgG, asialofetuin, asialo-beta 2-glycoprotein I and, likewise, synthetic glycoproteins as a lectin, exhibiting binding specificity for terminal galactosyl residues of the glycoprotein glycans. Binding of CRP to IgA, IgM, IgG, asialofetuin, asialo-beta 2-glycoprotein I and to synthetic glycoproteins requires immobilization onto surfaces of both CRP and the ligand. Fibronectin and fibrinogen are bound by surface-immobilized CRP also in soluble phase. Comparing various mono-, di-, and trisaccharides as competitive inhibitors of the lectin binding activity of CRP, only beta-D-Gal-(1-3)-D-GalNAc, beta-D-Gal-(1-4)-D-GalNAc, and beta-D-Gal-(1-4)-beta-D-Gal-(1-4)-D-GlcNAc had significant inhibitory power at a concentration of 8 mmol/liter. Binding activity of CRP was pH-dependent with an optimum at pH 5 to 6 and was reduced by 90% when pH was shifted from 6 to the physiologic pH value of 7.4. CRP exhibited lectin-like properties with binding specificity for galactosyl residues also when bound to K-562 erythroleukemia cells. It is therefore suggested that CRP immobilized onto surfaces exhibits lectin activity toward galactosyl groups preferentially in a mildly acidic environment as present at sites of inflammation.
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PMID:Lectin specificity and binding characteristics of human C-reactive protein. 162 92

NZW x BXSB F1 (W/B F1) male mice develop systemic lupus-like disease, and several autoantibodies, circulating immune complexes, and lupus nephritis become apparent. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction and thrombocytopenia due to the presence of both platelet-associated antibodies and circulating antiplatelet antibodies in this animal has been reported. We found that W/B F1 male mice produced autoantibodies against cardiolipin (aCL) and that the titer of aCL increases with age. aCL from W/B F1 male mice were mainly IgG and binding activity to cardiolipin was aCL-cofactor (beta 2-glycoprotein I (beta 2-GPI)) dependent. We developed monoclonal aCL from these animals and examined specificity of the autoantibodies. All the mAb used reacted with the negatively charged phospholipids, cardiolipin, phosphatidylserine, and phosphatidylinositol, and some reacted with platelets and DNA. The addition of human or mouse beta 2-GPI enhanced the titer for monoclonal aCL from the W/B F1 mice. From the results of competitive inhibition enzyme immunoassay with monoclonal aCL and purified beta 2-GPI, aCL from the W/B F1 mice recognized the complex of CL and beta 2-GPI. The W/B F1 male mouse may be an appropriate model for use in studies on the pathologic significance of aCL in patients with antiphospholipid syndrome.
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PMID:Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome. 163 62

Apolipoprotein H (APOH) (beta-2-glycoprotein I) polymorphism has been studied in 1159 Asians. The sample included 872 Chinese, 179 Asiatic Indians (Dravidian), 91 Filipinos, and 17 Malays. APOH polymorphism was determined by isoelectric focusing of sera in thin-layer polyacrylamide gels containing 3 M urea followed by immunoblotting. The frequencies of the three alleles--APOH*1, APOH*2, and APOH*3--were found to be 0.031, 0.900, and 0.069 in the Chinese; 0.061, 0.866, and 0.073 in the Dravidian Indians; 0.055, 0.923, and 0.022 in the Filipinos; and 0.088, 0.882, and 0.029 in the Malays. The phenotypic distribution was at Hardy-Weinberg equilibrium in all the populations.
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PMID:Apolipoprotein H (beta-2-glycoprotein I) polymorphism in Asians. 164 27

The nucleotide and complete amino acid sequence for the human beta 2-glycoprotein I (beta 2I) was derived by sequencing the cDNA clone pB2I-1. In addition to the 326 amino acid residues of the mature protein this clone codes for a putative leader peptide and contains sequence representing 5' and 3' untranslated regions. When this amino acid sequence was compared with the previously published primary sequence, three major amino acid substitutions were found, two involving cysteine residues. These substitutions lead to a new alignment of the complement control protein (CCP) repeats present in beta 2I and a prediction of the complete disulphide bond organization. Northern-blot analysis indicates that hepatocytes are a major site of biosynthesis for this protein. A transcription signal of about 1.5 kb was detected by using RNA from HepG2 cells.
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PMID:Complete nucleotide and deduced amino acid sequence of human beta 2-glycoprotein I. 165 Jan 81


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