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)

Antiphospholipid antibody, measured by enzyme-linked immunosorbent assay (ELISA) or by radioimmunoassay, and the lupus anticoagulant represent similar but different tests. The ELISA is now well standardized. It is at least partly, and possibly primarily, dependent on the presence of a cofactor, beta 2-glycoprotein I. Tests for both antiphospholipid antibody by ELISA and lupus anticoagulant should be performed in patients suspected of having this syndrome.
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PMID:Antiphospholipid antibodies: method of detection. 128 80

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.
Lupus 1992 Feb
PMID:A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. 130 67

Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta 2-glycoprotein I (beta 2GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified beta 2GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to beta 2GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if beta 2GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications.
Lupus 1992 Feb
PMID:Antiphospholipid antibodies differ in aPL cofactor requirement. 130 68

Anticardiolipin antibodies (aCL) were recently discovered to recognize a complex consisting of phospholipids and apolipoprotein H (apo H). In this study, we determined the serum apo H levels in 36 systemic lupus erythematosus (SLE) patients with or without antiphospholipid antibodies (aPL), including aCL and lupus anticoagulants, to clarify the possible effects of aPL on apo H levels in vivo. The apo H levels were low in SLE patients as compared with 22 healthy controls. However, no associations were found between apo H levels and circulating aPL or clinical features of the antiphospholipid antibody syndrome. A secondary hyperlipidemic state, which probably related to lupus nephritis (proteinuria) and/or prednisolone treatment, increased apo H levels in SLE patients.
Lupus 1992 May
PMID:Serum apolipoprotein H levels in systemic lupus erythematosus are not influenced by antiphospholipid antibodies. 130 75

The lipid-binding inhibitor of coagulation, beta 2-glycoprotein I (beta 2GPI), has been shown to form the antigen to which some autoantibodies against anionic phospholipids (aPL) are directed. Six murine monoclonal antibodies (MAbs) of the IgG1 isotype were raised against human beta 2GPI and could be subdivided into three groups on the basis of mutual competition experiments. MAbs 9G1 and 8C3 (group A) markedly inhibited the binding of immunoglobulins from aPL-positive sera to beta 2GPI-coated wells. Using a lipid-based solid-phase radioimmunoassay, the MAbs interacted with both anionic phospholipids and phosphatidylethanolamine, but not phosphatidylcholine, in a beta 2GPI-dependent manner. A cross-reaction between beta 2GPI from several (including bovine) species was seen with one of the MAbs (9G1). All six MAbs induced dose-dependent prolongation of the DAPTT, DRVVT, KCT and TTI clotting times of human plasma, whereas 9G1 was the sole antibody to be inhibitory with plasma from bovine origin. Synergistic inhibitory effects were observed with MAbs used in pairs provided that they did not compete with each other for beta 2GPI binding. The anticoagulant activity of the MAbs was fully neutralized by the addition of freeze-thawed platelets. The MAbs described here resemble lupus anticoagulants in several respects which makes them valuable to study the involvement of beta 2GPI in the autoimmune thrombotic pathophysiology.
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PMID:Lupus-like anticoagulant properties of murine monoclonal antibodies to beta 2-glycoprotein I. 138 49

Complexes formed by the interaction of negatively charged phospholipids and beta 2-glycoprotein I (beta 2-I) are the target of autoantibodies in systemic lupus erythematosus. The highly positively charged fifth (C-terminal) domain of human beta 2-I was produced as a fusion protein in an Escherichia coli expression system and was shown to bind to the negatively charged phospholipid, cardiolipin, almost as well as the intact protein. In an attempt to define the 3D structure of this domain, the disulphide linkage pattern was determined and shown to be Cys 1-4, Cys 2-5 and Cys 3-6 in contradiction to an earlier report. In the light of this information, the sequence of the fifth domain of beta 2 I (beta 2-I-5) is readily aligned with that of the 16th repeat of factor H, of which the 3D structure is known, and a model of beta 2I-5 has been built by homology. On the basis of the model we suggest residues that might be the target of profitable site-directed mutagenesis in structure-function studies.
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PMID:Activity, disulphide mapping and structural modelling of the fifth domain of human beta 2-glycoprotein I. 142 88

Plasmas of 16 patients positive for both IgG anticardiolipin (aCL) antibodies and lupus anticoagulant (LA) antibodies were subjected to adsorption with liposomes containing cardiolipin. In 5 of these plasmas both the anticardiolipin and the anticoagulant activities were co-sedimented with the liposomes in a dose-dependent manner, whereas in the remaining cases only the anticardiolipin activity could be removed by the liposomes, leaving the anticoagulant activity (LA) in the supernatant plasma. aCL antibodies purified from the first 5 plasmas were defined as aCL-type A, while the term aCL-type B was used for antibodies in the other 11 plasmas, from which 2 were selected for this study. Prolongation of the dRVVT was produced by affinity-purified aCL-type A antibodies in plasma of human as well as animal (bovine, rat and goat) origin. aCL-type B antibodies were found to be devoid of anticoagulant activity, while the corresponding supernatants containing LA IgG produced prolongation of the dRVVT only in human plasma. These anticoagulant activities of aCL-type A and of LA IgG's were subsequently evaluated in human plasma depleted of beta 2-glycoprotein I (beta 2-GPI), a protein which was previously shown to be essential in the binding of aCL antibodies to anionic phospholipids. Prolongation of the dRVVT by aCL-type A antibodies was abolished using beta 2-GPI deficient plasma, but could be restored upon addition of beta 2-GPI. In contrast, LA IgG caused prolongation of the dRVVT irrespective of the presence or absence of beta 2-GPI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticoagulant activity of beta 2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies. 144 Apr 95

Despite the striking clinical manifestations associated with antiphospholipid antibodies (aPL) the role of these autoantibodies in disease and the nature of their true "inducing" and "target" antigens remain elusive. To address these issues, we investigated the immunogenic potential of phospholipid structures. To date, phospholipid immunogens have included hexagonal (II) forms of phosphatidylethanolamine and mixtures of apolipoprotein H (beta 2-glycoprotein I) with cardiolipin. Both hexagonal (II) phosphatidylethanolamine and the cardiolipin/apolipoprotein H mixture were capable of inducing aPL with lupus anticoagulant activity. Bilayer phosphatidylethanolamine and cardiolipin in the absence of apolipoprotein H were nonimmunogenic. Our data support our views that specific phospholipid structures are recognized by the immune system and that such structures serve as inducing and/or target antigens in the pathogenesis of aPL in vivo.
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PMID:The nature of antiphospholipid antibodies. 149 1

The clinical and serological features of 38 aCL-positive patients were compared to those of 45 aCL-negative patients. A significantly higher incidence of thrombophlebitis and livedo reticularis was found in aCL-positive patients. There were 13 aCL positive patients with thrombophlebitis and/or arterial thromboses and these 13 patients were designated as having the antiphospholipid syndrome (APS) while the remaining 70 patients were diagnosed as having Systemic Lupus Erythematosus (SLE). APS patients also had a high incidence of arterial occlusions, recurrent abortions and strokes compared to SLE patients. Patients with high levels of IgG-aCL were more likely to have APS, while patients with low levels of IgG-aCL or IgM-aCL only were more likely to have SLE without the clinical features of APS. Since aCL antibodies have recently been shown to interact with a phospholipid-binding plasma protein beta 2-glycoprotein-I (beta 2-GPI), we measured the beta 2-GPI levels in these patients and found that beta 2-GPI levels are significantly higher in APS compared to SLE patients negative for aCL antibodies. Since beta 2-GPI is known to exert multiple effects on coagulation processes the interaction of aCL antibodies with this glycoprotein may play a pathogenic role in APS.
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PMID:Patients with anticardiolipin antibodies with and without antiphospholipid syndrome: their clinical features and beta 2-glycoprotein-I plasma levels. 151 96

Antiphospholipid antibodies (aPL) are defined by anticardiolipin antibody (aCL) ELISA and prolongation of phospholipid dependent coagulation assays (lupus anticoagulant; LAC). For the binding of aCL to cardiolipin a cofactor, beta 2-glycoprotein I (beta 2-GPI), is necessary. We have investigated whether the same cofactor is essential for LAC activity. Plasma from 6 LAC positive patients and 3 controls was depleted from beta 2-GPI by means of affinity chromatography. From the 6 LAC positive plasmas, 4 became LAC negative (tested with dRVVT) when beta 2-GPI was depleted and became positive again when purified beta 2-GPI (200 micrograms/ml) was added. A dose response curve showed that addition of 50 micrograms/ml beta 2-GPI to beta 2-GPI deficient patient plasma, led to a positive dRVVT. Depletion of, and addition of beta 2-GPI to plasma from controls had no effect on the dRVVT. Measurement of beta 2-GPI plasma levels in 19 LAC positive patients, 40 LAC negative patients and 15 controls showed no difference in beta 2-GPI levels. These results show that a combination of aPL and beta 2-GPI is essential not only for binding to cardiolipin, but also for LAC activity and imply that low beta 2-GPI levels (less than 50 micrograms/ml) can lead to false negative LAC tests. These observations may lead to new insights in the pathophysiological complications associated with aPL.
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PMID:Lupus anticoagulant activity is frequently dependent on the presence of beta 2-glycoprotein I. 151 7


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