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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between presence of anti-beta2-glycoprotein I autoantibodies (abeta2-GPI) and history of thrombosis is now widely known. However, differences in the methodology of abeta2-GPI detection have made the comparison of data from different laboratories extremely difficult. We discuss the significance of abeta2-GPI of the IgG, IgM and IgA isotypes, and our approach to developing an easier and more reproducible method for the detection of this autoantibody. In addition, we present data that shows that commercially available enzyme immunoassay plates differ regarding detectability of abeta2-GPI. Since the clinical significance of this heterogeneity is presently unclear, the set-up of the detection systems and interpretation of data need great care.
Lupus 1998
PMID:Anti-beta2-glycoprotein I antibodies. 981 83

It is widely hypothesized that autoantibodies directly contribute to the prothrombotic state in the antiphospholipid syndrome (APS). The discovery that antiphospholipid autoantibodies are specific for phospholipid-binding plasma proteins (beta2-glycoprotein I, prothrombin, etc.) has allowed a much more precise investigation of the interactions of autoantibodies and antigens, and the effects of these interaction on hemostasis. Recent studies suggest that two types of interactions may be important in the pathophysiology of APS: (1) antibody cross-linking of membrane bound antigens may alter the kinetics of phospholipid-dependent reactions; and (2) antibody cross-linking of antigens bound to cell surface receptors may trigger signal transduction and cellular activation. In light of these findings, previous reports implicating various mechanisms of autoantibody-mediated thrombosis are being re-evaluated.
Lupus 1998
PMID:Mechanisms of autoantibody-mediated thrombosis. 981 87

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to beta2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.
Lupus 1998
PMID:Atherosclerosis and the antiphospholipid syndrome: a link unravelled? 981 92

Antiphospholipid syndrome is characterized by a prothrombotic state and the presence of beta2-glycoprotein I (beta2-GPI)-dependent antiphospholipid antibodies. The feasibility of a B cell tolerance-based approach for specific reduction of anti-beta2-GPI antibodies was investigated. Anti-beta2-GPI antibodies isolated from a patient with antiphospholipid syndrome were used to screen peptide libraries expressed in phage, resulting in the identification of a phage that specifically bound anti-beta2-GPI antibodies. The phage-displayed peptide was identified and chemically optimized to generate a synthetic 14-mer peptide with an internal thioether linkage (LJP 685) that retained the binding profile of the original phage. LJP 685 was conjugated to a defined, non-immunogenic organic platform to generate a tetravalent presentation of LJP 685 for use as a toleragen. Tetravalent LJP 685 induced a dose-dependent reduction in antibody levels in mice previously immunized and boosted with LJP 685 coupled to the carrier keyhole limpet hemocyanin. These experiments support the technical feasibility of a tolerance-based approach for reducing anti-beta2-GPI antibodies in vivo.
Lupus 1998
PMID:A chemically defined, toleragen-based approach for targeting anti-beta2-glycoprotein I antibodies. 981 97

Anti-beta2-glycoprotein I (beta2-GPI) antibodies behave as classical Lupus Anticoagulants (LA), as they inhibit phospholipid-dependent coagulation reactions and their activity disappears in the presence of excess exogenous phospholipids (PLs). We have recently shown that a certain amount of PLs in the dilute Russell Viper Venom Time (dRVVT) test system is required to express LA activity of anti beta2-GPI antibodies. We have now extended this observation to two other tests, i.e., Kaolin Clotting Time (KCT) in which PLs are not added, and Tissue Thromboplastin Inhibition test (TTI) in which PLs are extremely diluted. In fact, affinity-purified antibody preparations from 5 patients with antiphospholipid syndrome did not express or only weakly expressed anticoagulant activity in both tests; the mean ratios of coagulation times obtained with purified antibodies and that of control buffer were 1.11 and 1.0 for KCT and TTI, respectively. On the contrary, the mean ratios in dRVVT were 1.31 and 1.49 at a PLs dilution of 1:8 and 1:64, respectively. Therefore, the presence of LA activity due to autoantibodies to beta2-GPI is characterized by a positive dRVVT and negative or only weakly positive KCT and TTI.
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PMID:dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-beta2-glycoprotein I autoantibodies. 1006 2

Antiphospholipid Syndrome (APS) was first described by Hughes and sometimes called as Hughes syndrome. Recent studies revealed that the antigen to anticardiolipin antibody (aCL) is not cardiolipin itself but co-factor beta 2-GPI which expresses its epitope when it combines cardiolipin or gets oxidized. Lupus Anticoagulant is now possibly considered as anti-prothrombin antibody. Livedo including Snedden syndrome, pulmonary hypertension and skin ulcer became considered as the part of symptoms of this disease. In ISAPA 1998, it is reported from several laboratories that IgA aCL is also pathogenic to thrombosis as well as IgG aCL. Atherosclerosis is also accelerated by aCL. Catastrophic APS is rare but fatal, reported 3 cases in Japan and 50 cases in the world.
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PMID:[Antiphospholipid syndrome]. 1007 9

In this study we determined the prevalence and clinical associations of immune-complexes-containing beta-2-glycoprotein I (beta2GPI) in randomly selected SLE patients. We studied 38 consecutive SLE patients attending the Rheumatology Unit. Previous arterial or venous-thrombosis were documented by the appropriate diagnostic test. Lipid profile including total cholesterol, LDL, VLDL, HDL and Lp(a) levels were determined from the sera of the fasting patients. Antibodies to cardiolipin, oxidized LDL and beta2GPI were detected employing ELISA. Beta2GPI containing IgG immune-complexes were assayed by using a dot-blot assay. Fourteen SLE patients (36.8%) were found to be positive for the presence of IgG anti-beta2GPI antibodies. Ten of the SLE patients (26.3%) were found to have high levels of beta2GPI containing immune-complexes. There was a positive correlation between beta2GPI-IC levels and the occurrence of thrombocytopenia in the patients (P < 0.05). Furthermore, patients with SLE and venous thrombosis had higher levels of beta2GPI-IC when compared with thrombosis-free patients or with healthy controls (P < 0.05). Patients with higher Lp(a) levels (> 50 mg/dl) possessed higher levels of beta2GPI-IC as compared with patients with lower Lp(a) concentration (< 20 mg/dl) (P < 0.05). These results suggest that IC-containing beta2GPI can help in defining a subpopulation of SLE patients with increased risk of thrombocytopenia and further aid in resolving mechanisms of immune-mediated tissue damage.
Lupus 1999
PMID:Beta2 glycoprotein I containing immune-complexes in lupus patients: association with thrombocytopenia and lipoprotein (a) levels. 1019 5

Antiphospholipid syndrome (APS) is defined by the presence of aPL antibodies in patients with thromboembolic phenomena. Some antiphospholipid (aPL) antibodies, such as those directed against beta2-glycoprotein I (beta2GPI), are associated with thromboembolism, possess Lupus Anticoagulant (LA) activity and recognize their target antigen only when bound to specific surfaces or to phospholipids (PL). To ascertain whether both free and antibody-bound beta2GPI circulate in APS, we set up an ELISA to detect [IgG anti-beta2GPI-beta2GPI] immune complexes. In this system, rabbit anti-human beta2GPI antibodies were adsorbed onto plastic plates, incubated with patient plasma, and bound complexes were detected by means of alkaline phosphatase-labeled goat anti-human IgG; each assay was stopped when positive controls consisting of in vitro generated immune complexes reached an Optical Density (OD) of 0.5 at 405 nm. Plasma from 16 patients with APS showed a mean OD405 of 0.291 (range 0.115-0.558), not statistically different from the mean obtained for 15 age- and sex-matched healthy volunteers (mean OD405 = 0.169, range 0.066-0.264). Surprisingly, levels of immune complexes in 14 patients with other autoimmune diseases and no circulating anti-beta2GPI antibodies were statistically higher (mean OD405 = 0.552, range 0.204-0.991) than those of healthy subjects and patients with APS. These data indicate that while autoantibodies to beta2GPI are mainly unbound in plasma of patients with APS, they are complexed with their antigen in patients with other autoimmune diseases, possibly reflecting a higher binding affinity.
Lupus 1999
PMID:[Anti-beta2 glycoprotein I-beta2 glycoprotein I] immune complexes in patients with antiphospholipid syndrome and other autoimmune diseases. 1019 6

Systemic Lupus Erythematosus (SLE) patients experience premature atherosclerosis. A deranged lipid metabolism and use of immunosuppressive medications accounts partially for the accelerated process. The role of autoimmunity in atherosclerosis has recently been highlighted. Autoantigenic determinants thought to play a role in the development of atherosclerosis include: modified lipoproteins, heat shock proteins and beta2-glycoprotein I (a target of 'autoimmune' anticardiolipin antibodies). In this present work we determined autoimmune markers which may be associated with premature atherosclerotic process found in SLE patients. We have found that antibodies to oxLDL were raised in the sera of lupus patients and cross-reacted with cardiolipin and with beta2GPI. OxLDL containing immune-complexes of the IgG and IgM isotypes were both elevated in the SLE patients as compared with healthy controls. Patients with high Lipoprotein (a) concentrations (>30 mg/dl) had higher levels of IgM oxLDL-containing immune-complexes. IgM but not IgG anti-HSP-65 antibodies were elevated in the lupus patients and levels of oxLDL containing immune-complexes correlated positively with the presence of anti-HSP 65 antibodies. Lysophosphatidylcholine (LPC) is a peroxide-derivative formed during LDL oxidation, was shown to evoke a humoral response in healthy subjects. Antibodies to lysophosphatidylcholine of the IgG but not the IgM isotype were reduced in SLE patients compared with controls, suggesting it may be 'consumed' into oxLDL containing immune complexes. Therefore, SLE patients exhibit a humoral autoimmune response towards the antigenic candidates incriminated in the progression of atherosclerosis. These findings may help identify factors that are involved in accelerating atherogenesis in SLE patients.
Lupus 1999
PMID:Atherosclerosis-related markers in systemic lupus erythematosus patients: the role of humoral immunity in enhanced atherogenesis. 1034 15

Lupus anticoagulants (LA) are immunoglobulins directed to either prothrombin or Beta-2-glycoprotein 1(beta1GPI) bound to phospholipids. Most patients with LA have both beta2GPI- and prothrombin-dependent antibodies. Several recent reports have shown that LA is more strongly associated with thrombosis than anticardiolipin antibodies (aCL). Therefore, an accurate detection of LA is of utmost importance in patients suspected of an antiphospholipid syndrome. We recently raised a series of murine monoclonal antibodies against human Beta-2-glycoprotein I (beta2GPI) with LA activity similar to affinity purified human beta2GPI-dependent LAs. A normal plasma pool, and the same pool spiked with LA positive anti-beta2GPI antibodies at two potency levels, were used as materials in an external quality assessment scheme organised by the European Concerted Action on Thrombosis (ECAT). Fifty nine laboratories participating in this trial were asked to test for the presence of a LA in the 3 samples submitted. The majority (82%) of the participants found the high potency LA sample to be positive. Only 37% of the laboratories considered the weak potency LA sample to be positive. The submission of a normal sample, a weakly positive sample and a clearly positive sample enabled us to compare the relative LA responsiveness of the different screening assays used. Clotting time ratios varied from 0.81 to 3.28 for sample B and from 0.66 to 5.32 for sample D. In general, the highest clotting time ratios were found with the dilute prothrombin time (dPT), the dilute Russell Viper Venom time (dRVVT) and the Kaolin Clotting time. The most frequently used screening tests were the aPTT and the dRVVT. With the various assay systems, LA responsiveness varied largely according to the reagents used. For the beta2GPI-dependent LA used in this study, PTT LA clearly showed the highest responsiveness among the aPTT reagents and Innovin among the dPT reagents. The present study also shows that many laboratories still rely on poorly responsive screening assays for their LA tests. Other laboratories rely on sensitive and more specific integrated test systems based on a sensitive screening assay with a low phospholipid content and a confirmatory test employing high phospholipid concentrations. The most used integrated system was dRVVT based. However, also here the LA responsiveness was largely reagent dependent. In conclusion, many laboratories still rely on poorly responsive screening assays by which weakly positive LA samples are misdiagnosed. LA positive anti-beta2GPI moabs have a potential for the unlimited production of LA control specimens, that may help hemostasis laboratories choose more LA responsive assay systems and to assess intralaboratory precision of their LA testing.
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PMID:Lupus anticoagulant testing in Europe: an analysis of results from the first European Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta2-glycoprotein I. 1040 70


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