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)

Anticardiolipin antibodies (aCL) purified from patients with autoimmune disease have recently been shown to interact with a phospholipid-binding plasma protein, beta 2-glycoprotein I (beta 2-GPI). The aim of this study was to determine whether aCL purified from patients with infection also interact with beta 2-GPI. aCL purified from 23 patients with malaria, infectious mononucleosis, tuberculosis, hepatitis A or syphilis did not require the presence of beta 2-GPI to bind cardiolipin (CL). In contrast, aCL were purified from 11 out of 12 patients with autoimmune disease that bound CL only in the presence of beta 2-GPI. Thrombotic complications appear to be associated with aCL occurring in autoimmune disease but not with aCL associated with infections. We postulate that this increased risk of thrombosis in the autoimmune group may be due to the presence of aCL that bind CL in association with beta 2-GPI, a plasma protein with anticoagulant activity.
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PMID:A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. 130 67

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.
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PMID:Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. 152 18

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

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

Human beta 2-glycoprotein I (beta 2-GPI) is involved in cardiolipin (CL) binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). We examined the inter-species differences of beta 2-GPI in alternation of CL binding of aCL. beta 2-GPI preparations were obtained from human, bovine, and rat sera by sequential CL--polyacrylamide affinity, DEAE--cellulose, and anti-human IgG-conjugated Sepharose CL-4B column chromatography, and they had apparent molecular weights of 50, 53, and 55 kDa respectively. Human beta 2-GPI not only enhanced CL binding by aCL in SLE but also depressed it by those in syphilis. Either bovine and rat beta 2-GPI exerted no or quite small inhibition of the binding of syphilitic aCL compared with human beta 2-GPI whereas all three species of beta 2-GPI generated binding of aCL in SLE to a similar degree. Further, a complete cDNA clone, p beta 2-GPI, was isolated from a human hepatoma cell line, HepG2, and its nucleotide sequence was analyzed. The sequences of bovine and rat counterpart molecules (beta 2-GPI) are highly homologous to that of the deduced sequence, and their corresponding regions are 84.0 and 82.5% identical to the complete domain and to the amino acid sequence 53-326 of human beta 2-GPI respectively. One of major differences appears at position 154 in human beta 2-GPI, and might be associated with the inhibitory effect on the binding of syphilitic aCL. The sequencing analysis of these beta 2-GPI proteins might provide leads to functional sites of domains which would be associated with such serological phenomena.
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PMID:Molecular definition of human beta 2-glycoprotein I (beta 2-GPI) by cDNA cloning and inter-species differences of beta 2-GPI in alternation of anticardiolipin binding. 177 18

We investigated whether or not the use of Tween 20 could help to distinguish beta 2-glycoprotein I (GPI) independent anticardiolipin antibody (aCL) (syphilis-type aCL) from GPI-dependent aCL (SLE-type aCL) in a GPI-dependent/independent aCL ELISA. aCL was positive in all 16 SLE patients and all 15 syphilis patients, who were positive for aCL in the standard ELISA, in the GPI-independent ELISA with Tween 20. GPI-dependent aCL was detected in 12/16 SLE patients by the GPI-dependent ELISA with Tween 20. aCL was not detected in any of the syphilis patients by GPI-dependent ELISAs. On the basis of these results, we recommend that Tween 20 should be used in ELISAs to distinguish GPI-dependent aCL from GPI-independent aCL.
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PMID:Distinguishing beta 2-glycoprotein I dependent (systemic lupus erythematosus type) and independent (syphilis type) anticardiolipin antibody with Tween 20. 794

Anti-phospholipid antibodies (aPL), in the form of anti-cardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC), are found in a number of disorders, including systemic lupus erythematosus. Autoimmune aPL are associated with clinical manifestations that may include vascular thrombosis, recurrent fetal loss, thrombocytopenia, livedo reticularis and neurological abnormalities. aPL found in the context of infections such as syphilis are not usually associated with clinical complications. Here we report the presence of aCL in Brown Norway (BN) rats treated with mercuric chloride (HgCl2), which is known to induce a number of other autoantibodies. Some also showed LAC activity as shown by extension of the kaolin clotting test time. The binding of human autoimmune aPL is known to be considerably enhanced by a serum cofactor, beta 2-glycoprotein I; only slight enhancement, and in some cases inhibition, was found with BN rat aPL. These results indicate that aPL can be added to the list of autoantibodies that have been documented in the HgCl2 treated BN rat. The effect of addition of serum co-factor suggests that these are most closely related to human infection-associated (as opposed to autoimmune) aPL.
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PMID:Anti-phospholipid antibodies in the mercuric chloride treated brown Norway rat. 798 Aug 48

We investigated the prevalence of various autoantibodies [anti-cardiolipin antibody (aCL), lupus anticoagulant (LA), immune complexes (ICs), anti-nuclear antibody (ANA), and anti-deoxyribonucleic acid antibody (aDNA)] in hemophiliac individuals with (n = 50) and without (n = 42) infection by human immunodeficiency virus type 1 (HIV-1). The positivity rate for ANA was similar in both groups, and none of the patients was positive for LA and aDNA. aCL was positive in 35 of 50 (70%) HIV-1-positive hemophiliac individuals and 33 of 42 (79%) HIV-1-negative hemophiliac individuals. However, the majority of the aCL was revealed to be beta 2-glycoprotein I independent, thus corresponding to a syphilis type aCL that does not cause the so-called antiphospholipid syndrome. A total of 39 of the 45 HIV-1 positive hemophiliac individuals (87%) and 34 of 41 HIV-1-negative hemophiliac individuals (83%) had at least one type of IC [C1q-, C3d-, and/or murine monoclonal rheumatoid factor (mRF)- IgG]. The mechanism producing various autoantibodies in hemophiliac persons irrespective of their HIV-1 status is still unclear, but pathogens (e.g., HIV-1, hepatitis B, and hepatitis C) and alloantigens in the blood products that these patients require may be possible candidates. The clinical significance of the presence of these autoantibodies and the underlying mechanisms involved both need to be clarified further.
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PMID:High prevalence of anti-cardiolipin antibody, C1q-, C3d-, and mRF-IgG immune complexes, and anti-nuclear antibody in hemophiliacs irrespective of infection with human immunodeficiency virus type 1. 841 Jun 68

The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important.
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PMID:Functional effects of anticardiolipin antibodies. 890 63

The family of antiphospholipid antibodies includes antibodies binding to cardiolipin in serological test for syphilis, antibodies prolonging the clotting time in lupus anticoagulant test, antibodies reacting with plasma phospholipid-binding proteins, such as beta 2-glycoprotein I and prothrombin, and antibodies binding to oxidized low-density lipoprotein (LDL). Antiphospholipid antibodies are traditionally associated with arterial and venous thrombosis in patients with primary or secondary antiphospholipid syndrome. The recent studies, especially those on patients with myocardial infarction, extend the concept of antiphospholipid antibodies, and suggest that they play a role also in atherosclerosis. Based on the clinical studies and immunological findings, it seems that the differences in the specificity of antiphospholipid antibodies may reflect to their pathogenetic mechanisms and, finally, to their clinical consequences. The present review suggests that antibodies to oxidized LDL may not interfere directly with blood coagulation, but seem to have importance in the inflammation of the vessel wall in atherosclerosis and in vasculitis. Instead, antibodies to beta 2-glycoprotein I and to prothrombin show a closer association with thrombosis. It is possible that in the atherosclerotic plaque, the plasma proteins, such as beta 2-glycoprotein I or prothrombin, are bound to the endothelial surface and antibodies to cryptic epitopes revealed in these proteins are induced. These antibodies may contribute to the formation of atherosclerotic thrombosis by changing the balance of haemostasis toward hypercoagulative state.
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PMID:Antiphospholipid antibodies and atherosclerosis. 890 78


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