Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In September 1991, an NIH workshop on molecular and biological aspects of antiphospholipid antibodies (aPL) identified questions for future studies: are the antibodies defined by the ELISA and by the lupus anticoagulant tests the same? Is aPL directly responsible for disease? What is the antigen? What drives the production of aPL? What is the role of beta 2-glycoprotein I? What accounts for patient heterogeneity? Can a satisfactory animal model be developed? The NIH workshop did not address important clinical questions, including those of pathogenesis and treatment. In 1994 many of these questions have at least partial answers. beta 2-glycoprotein I appears to be an obligatory component of the antigen, abnormal coagulation is the probable central pathogenic event and animal models now exist. There are still critical unknowns that define a future research agenda: the genetics of the aPL syndrome, the relationship of aPL to SLE and mechanisms of pathogenesis (including why clotting is episodic and what is the cellular or anatomical location of the initial injury). Despite a decade of clinical studies, risk prediction for defined patient groups is only now beginning to be studied. There are still almost no randomized, prospective, controlled treatment trials on any aspect of the syndrome nor are there definitive answers regarding which among antiplatelet, anticoagulant or antithrombin therapies is superior, what is the role of immunosuppressive therapy and what experimental therapies might be introduced. The molecular biology of the antigen-antibody interaction will soon be fully understood, then the cellular and the organism biology. Definitive treatment interventions may await this understanding but adequate therapies are available at this time to conduct important and effective prospective clinical trials.
 ...
PMID:Antiphospholipid antibody: future developments. 780 22

Beta 2-glycoprotein I (beta 2-GPI) binds negatively charged substances and inhibits intrinsic blood coagulation in the presence of ellagic acid-phospholipid suspension. Beta 2-GPI is thought to be an important protein in the reaction between negatively charged phospholipids and anti-phospholipid antibodies which appear in patients with lupus anticoagulant/antiphospholipid antibody syndrome. We prepared a monoclonal antibody against beta 2-GPI purified from human plasma and obtained beta 2-GPI-depleted plasma using a monoclonal antibody-coupled column. Either partial thromboplastin time or the activation of prekallikrein induced by diluted ellagic acid-phospholipid suspension in beta 2-GPI-depleted plasma was not different from that in control plasma. Beta 2-GPI inhibited the intrinsic blood coagulation only when added to control or beta 2-GPI-depleted plasma in excess (more than physiological concentrations). The intrinsic fibrinolysis in beta 2-GPI-depleted plasma induced by dextran sulfate was not impaired and, again, beta 2-GPI inhibited the intrinsic fibrinolysis only when added to control or beta 2-GPI-depleted plasma in excess. These results indicate that both in vitro Actin-induced intrinsic coagulation and dextran sulfate-induced fibrinolytic activities are significantly inhibited by more than physiological concentrations of beta 2-GPI.
 ...
PMID:Ellagic acid/phospholipid-induced coagulation and dextran sulfate-induced fibrinolytic activities in beta 2-glycoprotein I-depleted plasma. 786 69

The sera patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) were tested, by ELISA, for antibodies to phosphatidylethanolamine (aPE), as well as to cardiolipin (aCL) and compared to healthy blood donors (HBD). Both, SLE and APS patients presented a higher titre of IgM-aPE antibodies than normals, while the IgG and IgA aPE reactivity did not differ. APS patients were characterized by higher IgM-aPE antibody titres than SLE patients. In contrast, the predominant isotype of aCL antibodies in APS patients was IgG. The IgM aPE reactivity was correlated with IgM aCL reactivity, while no correlation was observed between the total IgM values and IgM-aPE binding units of sera tested. Since it was shown that beta 2-glycoprotein-I (beta 2-GPI) contributes to a complex antigen by binding to phospholipids and that this antigen is recognized by antiphospholipid antibodies from autoimmune patients, sera beta 2-GPI levels were measured and correlated to aCL and APE activity. Although APS patients had higher beta 2-GPI levels than SLE patients, no correlation was found between the beta 2-GPI levels and IgG/IgM aCL and IgM-aPE reactivities a finding suggesting that in addition to beta 2-GPI, other cofactors for aPE antibodies may exist. These findings indicate that aPE and aCL antibodies co-exist and that the IgM-isotype is predominant in APS. In addition, the IgA and IgG aPE antibodies appear to occur in low titres in these patients, as well as in normals and may exist as natural autoantibodies. We suggest that the high IgM-aPE antibodies may be viewed as a thymus independent process.
 ...
PMID:Antibodies to phosphatidylethanolamine in antiphospholipid syndrome and systemic lupus erythematosus: their correlation with anticardiolipin antibodies and beta 2 glycoprotein-I plasma levels. 802 4

Antiphospholipid antibodies are autoantibodies that can be detected in plasma or serum with phospholipid-dependent coagulation tests or solid-phase immunoassays. The presence of these autoantibodies is strongly associated with an increased risk for arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia. This paradoxical association of the in vitro prolongation of clotting assays and in vivo thrombosis has stimulated the search for the real antigen to which the autoantibodies are directed. A large number of potential pathological mechanisms have been proposed, and although disturbance of a certain metabolic pathway by the antibodies can explain a thrombotic tendency in one patient, no general pathological mechanism explaining thrombosis in the whole patient population has been found. This suggests that the antiphospholipid antibodies are a heterogeneous group of autoantibodies and is supported by the recent observations that antiphospholipid antibodies are not directed against phospholipids alone but against a combination of phospholipids and phospholipid-binding proteins. Both the phospholipid and the protein are part of the antigen. For the detection of antiphospholipids in an ELISA set-up, beta 2-glycoprotein I is the protein cofactor. In the coagulation tests, beta 2-glycoprotein, as well as prothrombin, can act as cofactor. However, the presence of these two proteins as a part of the epitope of the antiphospholipid antibodies does not explain the thrombotic tendency in the patient group. We have found that more physiologically relevant cofactors such as protein C and protein S, for which it is known that a partial deficiency is correlated with a thrombotic tendency, can also act as cofactors for the binding of antiphospholipid antibodies. It is concluded that antiphospholipid antibodies are a heterogeneous group of autoantibodies with varying affinity for different protein-phospholipid complexes and that inhibition of the biological activity of the protein part of the complex determines the pathological capacity of the antibodies.
 ...
PMID:Antiphospholipid antibodies: specificity and pathophysiology. 802 48

The amount and type of sialylation of tumor cell membranes depends on the activity of a number of different sialyltransferase enzymes. For the detection of specific activities in human colorectal carcinoma tissue several glycoprotein and glycolipid acceptors were used: desialylated fetuin, alpha 1-acid glycoprotein, beta 2-glycoprotein I, ovine submaxillaris mucin, and the gangliosides GM1, GM2, GM3 and GD1a. Because of their possible relevance for metastasis, precursors of Le(a) and Le(x) antigens, too, were employed, namely neoglycolipids produced by coupling LcOse4 or NeoLcOse4 oligosaccharides to L-alpha-phosphatidyl-ethanol-amine-dipalmitoyl. Our data indicate that human colorectal tumor tissue contains two highly active sialyltransferase enzymes, which are only weakly expressed in normal mucosa. These are a N-glycan-specific alpha 2,6-sialyltransferase, which was significantly increased in metastasizing tumors, and a Gal beta 1,3Gal-NAc-specific sialyltransferase, which was increased in tumors of early stages. A shift to enhanced alpha 2,6-sialylation of membrane glycoproteins during carcinogenesis was demonstrated by lectin ELISA analysis of magneto-bead separated tumor cells. Quantitative determination of specific sialyltransferase activities may be a sensitive tool for detection and monitoring of colon carcinoma.
 ...
PMID:Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors. 819

Beta 2 glycoprotein I (apolipoprotein H, beta 2GPI) is involved in the formation of epitope(s) recognized by clinically relevant autoantibodies from patients with antiphospholipid syndrome. We studied the binding of beta 2GPI to chemically activated polystyrene in a microtitre plate format. Adsorption isotherms (at 37 degrees C) were generated for beta 2GPI on activated polystyrene and on unactivated polystyrene, with both human serum antibodies and rabbit polyclonal IgG antibodies as probes, and horseradish peroxidase (HRP)-tagged anti-IgG to detect binding. Additionally, beta 2GPI was biotinylated and isotherms were developed by using HRP-streptavidin as the recognition sequence. Human serum autoantibodies, which did not precipitate beta 2GPI in solution, yielded a characteristic chemisorption isotherm on activated polystyrene but did not recognize beta 2GPI bound to untreated polystyrene. The rabbit IgG, which did precipitate beta 2GPI in solution, detected beta 2GPI bound to both activated polystyrene and, to a lesser extent, to untreated polystyrene. The binding of beta 2GPI to untreated polystyrene was confirmed by the use of biotinylated beta 2GPI. To assess the prevalence of IgG anti-beta 2GPI autoantibodies, we surveyed 113 sera submitted to our laboratory for anticardiolipin antibody (aCL) testing. Only nine (8%) had anti-beta 2GPI activity greater than two standard deviations above the mean for those sera in which aCL activity was within normal limits. We conclude that epitope presentation of beta 2GPI for human autoantibody binding is dependent on surface properties of the polystyrene, and that beta 2GPI autoantibodies are found only in a subpopulation of sera positive for aCL.
 ...
PMID:Binding of beta 2 glycoprotein I to activated polystyrene and its recognition by human IgG autoantibodies. 857 91

Autoimmune antiphospholipid antibodies are a hallmark of patients with antiphospholipid syndrome, and require a protein cofactor, beta 2-glycoprotein I, to bind anionic phospholipids. In these same patients, moreover, IgG directly binding beta 2-glycoprotein I are described. We found high plasma titres of both IgM and IgG anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome. After passing plasma through a Sephacryl S-300 column, an identical distribution pattern between anti beta 2- glycoprotein I and anticardiolipin antibodies was observed. Moreover, when IgG immunocomplexes were isolated from a high molecular fraction, IgM anti- beta 2-glycoprotein I and anticardiolipin antibodies were detected. Thus IgG, IgM ad IgG-IgM complexes of anti-beta 2-glycoprotein I antibodies are present at the same time in a patient with antiphospholipid syndrome.
 ...
PMID:Anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome. 860 82

We investigated the role of alpha IIb beta 3 in microparticle generation by normal and thrombasthenic platelets stimulated with collagen plus thrombin. Microparticle generation by normal platelets was scarcely inhibited by monoclonal antibodies for glycoprotein Ib and glycoprotein IX. Although one monoclonal anti-alpha IIb beta 3 antibody (NNKY1-32) partly inhibited microparticle generation, 3 other monoclonal anti-alpha IIb beta 3 antibodies had little effect. However, the combination of 4 monoclonal anti-alpha IIb beta 3 antibodies or treatment with a polyclonal anti-alpha IIb beta 3 antibody significantly inhibited microparticle generation (p < 0.05). Microparticle generation by thrombasthenic platelets also occurred after stimulation with collagen plus thrombin, although at a significantly lower level compared with normal platelets. Monoclonal antibodies for resting alpha IIb beta 3, P-selectin, activated alpha IIb beta 3 and beta 2-glycoprotein I bound to microparticles from healthy platelets. In contrast, only a monoclonal antibody for beta2-glycoprotein I bound to thrombasthenic microparticles. These results suggest that microparticle generation by collagen plus thrombin occurs via two different mechanisms which are dependent and independent of alpha IIb beta 3, respectively. The alpha IIb beta 3-dependent mechanism appears to require activation of alpha IIb beta 3.
 ...
PMID:Participation of alpha IIb beta 3 in platelet microparticle generation by collagen plus thrombin. 869 76

IgG antibodies to cardiolipin and beta 2-glycoprotein I were looked for using an enzyme-linked immunosorbent assay (ELISA) in 19 patients with giant cell arteritis (meeting 1990 American College of Rheumatology criteria), including 16 with concomitant polymyalgia rheumatica (meeting Bird's criteria) and in three patients with isolated polymyalgia rheumatica. IgG anti-cardiolipin antibodies were demonstrated in eight patients (36%) and IgG anti-beta 2-glycoprotein I antibodies in two patients (9%) including one without anti-cardiolipin antibodies. Titers of anti-cardiolipin antibodies ranged from 27 to 190 units of IgG antiphospholipid antibodies (UGPL) (mean 71 UGPL). Of the eight patients with anti-cardiolipin antibodies, two had giant cell arteritis without polymyalgia rheumatica and six had polymyalgia rheumatica with clinical (n = 2) or histologic (n = 4) evidence of giant cell arteritis. None of the three patients with polymyalgia rheumatica but no giant cell arteritis had anti-cardiolipin or anti-beta 2 glycoprotein I antibodies. The VDRL was negative in the 14 patients who had this test. Tests for lupus anticoagulant were performed routinely, always with negative results. Among giant cell arteritis patients, those who tested positive for anticardiolipin antibody had significantly higher values for the erythrocyte sedimentation rate (p < 0.006) and for serum C-reactive protein (p < 0.03) and fibrinogen values (p = 0.05), and a trend toward higher platelet counts, as compared to those who tested negative for anticardiolipin antibody. The mean daily prednisone dose at the time of sampling was significantly lower in giant cell arteritis patients with anti-cardiolipin antibodies (p < 0.05); this difference may account for the apparent correlation between anti-cardiolipin antibodies and laboratory markers for inflammation. These data, as well as findings from serial measurements, suggest that anti-cardiolipin antibodies are present early in the course of giant cell arteritis and disappear within a few weeks of initiation of corticosteroid therapy in a dose of more than 25 mg prednisone per day. In this study, only one patient without anticardiolipin antibodies developed a cerebrovascular accident. Positive tests for anti-cardiolipin antibody or anti-beta 2 glycoprotein I antibody in a patient with polymyalgia rheumatica suggest a diagnosis of concomitant giant cell arteritis, which is usually symptomatic.
 ...
PMID:Antibodies to cardiolipin and beta 2 glycoprotein I in patients with polymyalgia rheumatica and giant cell arteritis. 873 42

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.
 ...
PMID:Functional effects of anticardiolipin antibodies. 890 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>