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 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

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.
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PMID:[Anti-beta2 glycoprotein I-beta2 glycoprotein I] immune complexes in patients with antiphospholipid syndrome and other autoimmune diseases. 1019 6

Antibodies which bind beta2-glycoprotein I (beta2GPI) are associated with antiphospholipid syndrome. Synthetic peptide mimotopes have been discovered which compete with beta2GPI for binding to selected anti-beta2GPI. A thiol-containing linker was attached to the N-terminus of two cyclic thioether peptide mimotopes, peptides 1a and 1b. The resulting peptides, with linker attached, were reacted with two different haloacetylated platforms to prepare four tetravalent peptide-platform conjugates to be tested as B cell toleragens. The linker-containing peptides were reacted with maleimide-derivatized keyhole limpet hemocyanin (KLH) to provide peptide-KLH conjugates. Peptides 1a and 1b were also modified by acylation with 3-(4'-hydroxyphenyl)propionic acid N-hydroxysuccinimidyl ester. The resulting hydroxyphenyl peptides were radioiodinated and used to measure anti-peptide antibody levels. The KLH conjugates were used to immunize mice to generate an anti-peptide immune response. The immunized mice were treated with the conjugates or saline solution and boosted with the appropriate peptide-KLH conjugate. Three of the four conjugates suppressed the formation of anti-peptide antibody. The stabilities of the conjugates in mouse serum were measured, and the relative stabilities did not correlate with ability to suppress antibody formation.
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PMID:Multivalent thioether-peptide conjugates: B cell tolerance of an anti-peptide immune response. 1034 81

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

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

Antiphospholipid antibodies such as anticardiolipin antibodies and lupus anticoagulant are frequently detected in sera from patients with systemic lupus erythmatosus and from those with related autoimmune disorders. Thromboembolic manifestations, fetal losses or thrombocytopenia in association with antiphospholipid antibodies, are hallmarks of the antiphospholipid syndrome (APS). Recent studies indicates that anticardiolipin antibodies bind to beta 2-glycoprotein I and that a part of lupus anticoagulant binds to beta 2-glycoprotein I or to prothrombin. Antiphospholipid antibodies might induce thrombosis by altering the function of vascular endothelial cells or by accelerating the progression of atherosclerosis. Warfarin, heparin or low dose aspirin have been recommended to prevent recurrent episodes of thrombosis in patients with the APS.
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PMID:[The antiphospholipid syndrome]. 1042 70

We report the case of a young woman with primary antiphospholipid syndrome (APS), which presented with acute renal failure, hypoproteinemia, hypoalbuminemia and nephrotic proteinuria. Investigations showed total infarction of right kidney by extensive arterial and vein thrombosis and presence of anticardiolipin antibodies IgG isotype (anti-beta2-glycoprotein I-positive). She was submitted to right nefrectomy and initiated anticoagulant therapy. After nefrectomy, the postoperative period was marked by the development of arterial hypertension and persistence of nephrotic syndrome. Hypertension was treated with antihypertensive drugs (IECA, beta-blocker and calcium antagonist). As the nephrotic syndrome persisted despite anticoagulant and antihypertensive therapy, the patient was treated with oral corticosteroids. Her renal function improved, hypoproteinemia and hypoalbuminemia corrected to normal values and proteinuria decreased to subnephrotic value. We discuss the unusual presentation of this case of primary antiphospholipid syndrome with total unilateral renal thrombosis and nephrotic syndrome that respond to anticoagulant, antihypertensive and corticosteroid therapy.
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PMID:Primary antiphospholipid syndrome presented by total infarction of right kidney with nephrotic syndrome. 1044 98

The aim of this study was to determine if the measurement of anti-beta2-glycoprotein I antibodies (abeta2-GPI) in serum levels contributes to the better characterization of the clinical situation of patients with antiphospholipid syndrome (APS). For this purpose abeta2-GPI of both isotypes was measured in 42 patients with APS and 32 SLE patients without APS. Clinical records of all patients were thoroughly reviewed. The presence of abeta2-GPI was correlated with the clinical manifestations of APS and compared with the presence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) activity. There was a positive correlation between levels of aCL and abeta2-GPI for both IgG and IgM isotypes (rho of Spearman=0.82 and 0. 64 respectively, P=0.0001). Both antibodies presented significantly higher titres in LA positive patients (P<0.05). The specificity for APS was 91% for IgG abeta2-GPI vs 75% for IgG aCL and 87% for IgM abeta2-GPI vs 81% for IgM aCL. 68% of patients with thrombosis of 100% of patients with thrombocytopenia showed positive tests for all three markers (aCL, LA, abeta2-GPI). Simultaneous presence of circulating LA and high titres of both aCL and abeta2-GPI identify a subset of patients with primary APS (PAPS) who have a more severe clinical course of the disease. Although the specificity of abeta2-GPI IgG is higher than that of aCL IgG, when all three tests are performed abeta2-GPI testing provides only additional information to that of aCL and LA. Therefore, we concluded that the abeta2-GPI test should not be considered as a substitute for conventional LA or aCL assays. However, performance of abeta2-GPI seems to be important in PAPS with high aCL titres, to alert the physician about the risk for the worst course of the illness.
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PMID:Do antibodies to beta2-glycoprotein 1 contribute to the better characterization of the antiphospholipid syndrome? 1048 10

It is of considerable interest to ascertain whether a hollow fiber cartridge containing histidine immobilized on polyethylenevinyl alcohol membrane (His-PEVA) is able to retain specific autoantibodies involved in antiphospholipid syndrome. To this end diluted patient pathogenic plasma containing high levels of anti-beta2-glycoprotein I (anti-beta2GPI) and antiprothrombin antibodies was processed through the functionalized cartridge. The adsorbed material was then eluted under mild conditions and analyzed; an enrichment of the eluted fractions in total IgG and more specifically in IgG2 subclass was observed, compared with the injected sample. Enzyme-linked immunosorbent assay tests showed a higher specific binding of antiprothrombin and anti-beta2GPI in these fractions. This was in accordance with the concomitant higher anticoagulant activity measured on the same fractions. All in vitro results clearly demonstrated the ability of the His-PEVA cartridge to preferentially adsorb these autoantibodies. Hence the functionalized cartridge represents a potential tool for the treatment of antiphospholipid syndrome by selective extracorporeal removal of IgG.
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PMID:Functionalized hollow fiber membrane cartridge for adsorption of Anticofactor/Antiphospholipid antibodies: a potential tool for treatment. 1049 Oct 31

A 32-year-old male dialysis patient with lupus nephritis was admitted because of shunt obstruction. The arteriovenous fistula was reconstructed, but obstruction recurred twice within several hours after surgery. A high blood level of anticardiolipin beta2-glycoprotein I antibody suggested that shunt obstruction was caused by a thrombotic tendency related to the antiphospholipid antibody syndrome. Accordingly, for the third shunt procedure, antiplatelet therapy (which had been commenced for systemic lupus erythematosus) was combined with dalteparin sodium from before surgery and warfarin was added postoperatively. This regimen prevented shunt obstruction. In conclusion, hemodialysis patients who suffer repeated shunt obstruction should be examined for antiphospholipid antibody syndrome.
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PMID:A case of antiphospholipid antibody syndrome diagnosed after thrombosis of an arteriovenous shunt. 1053 10


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