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)

Relapsing polychondritis (RP) is an extremely rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM- and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG- and IgM-isotypes) and anti-beta-2-glycoprotein I-antibodies (a beta 2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated a beta 2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP.
Lupus 1998
PMID:Anti-phospholipid-antibodies in patients with relapsing polychondritis. 949 43

We studied the prognostic significance of antiphospholipid antibodies for recurrence of venous thromboembolism (VTE), in 71 patients admitted for acute VTE (deep-vein thrombosis or pulmonary embolism) in a single internal medicine unit. Lupus anticoagulant (LA), antibodies directed against beta 2-glycoprotein I (beta 2GPI) and antibodies against both beta 2GPI and a mixture of phospholipids (cardiolipin, phosphatidylserine and phosphatidic acid) (APAs) were measured. The patients were followed-up (mean 4.9 years) to determine the time to the next VTE. We found LA in nine patients, anti-beta 2GPI antibodies in seven patients and APAs in six patients. The cumulative risk of recurring VTE was higher in patients with beta 2GPI-binding antibodies (hazard ratio 12.6, 95% CI 1.5-104.9; p = 0.0029). The risk associated with APAs was 11.5 (95% CI 1.3-98.9; p = 0.0049) and that for LA was 3.7 (95% CI 0.9-15.6; p = 0.055). The risk of VTE recurring was higher both in patients with antibodies directed against beta 2GPI, and in patients with antibodies directed against beta 2GPI and a mixture of phospholipids, than in patients without these antibodies.
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PMID:Antibodies against phospholipids and beta 2-glycoprotein I increase the risk of recurrent venous thromboembolism in patients without systemic lupus erythematosus. 957 94

Lupus anticoagulant (LA) antibodies have been shown to be directed to protein-phospholipid complexes. In this study, we report on LA antibodies from patients with the 'antiphospholipid' syndrome (APS), that are directed to prothrombin and beta2-glycoprotein I, but not to the complexes of these plasma proteins to anionic phospholipids. The anti-prothrombin antibodies studied had different reactivities in two clotting assays: the dilute Russell's viper venom time (dRVVT) and the dilute kaolin clotting time (dKCT). Anti-prothrombin and anti-beta2-glycoprotein I (anti-beta2GPI) antibodies, affinity-purified from one patient with APS were not cross-reactive and had different effects in the dRVVT and dKCT clotting tests. Polyclonal anti-prothrombin antibodies, affinity-purified on a prothrombin column, from two patients with prothrombin reactivity in their plasma, have affinity constants to prothrombin of 104 and 192 nM. The patient with affinity-purified antibodies to prothrombin and beta2GPI, had affinity constants to prothrombin and beta2GPI, respectively, of 192 nM and 3030 nM, respectively. LA antibodies are a heterogeneous population of antibodies that have different immunological specificities and clotting test reactivities in different patients.
Lupus 1998
PMID:Anti-beta2-glycoprotein I and anti-prothrombin antibodies in patients with the 'antiphospholipid' syndrome: immunological specificity and clotting profiles. 969 36

Prolactin (PRL) is closely associated with autoimmune diseases in animal models and humans, and several disease-related autoantibodies were reported in increased titers in patients with hyperprolactinemia (HPRL). We studied the presence of anti-endothelial cell antibodies (AECA) and other autoantibodies in sera of female patients with HPRL. Sera from 25 HPRL patients and 10 healthy female controls were tested for AECA (against both macrovascular and microvascular endothelial cell antigens), anti-dsDNA, and anti-cardiolipin (anti-CL) using ELISA. Sera were considered positive for the autoantibody when the optical density (OD) value was more than 3 s.d. above the mean of the OD in normal controls. Sera from 13 patients were obtained repeatedly during dopaminergic anti-PRL treatment, to relate PRL level or anti-PRL treatment with the autoantibody levels. Elevated micro and/or macrovascular AECA were observed in sera from 19/25 patients (76%). Elevated titers of anti-CL Abs, all beta2-GPI-dependent, and low levels of anti-dsDNA antibodies (Abs) were also observed in the HPRL patients. Inhibition studies showed that the affinity purified AECAs bound the endothelial cell (EC) antigens in a dose-dependent manner. Titers of AECA as well as anti-DNA and anti-CL autoantibodies did not correlate with PRL level nor with the use or duration of anti-PRL treatment. None of the HPRL patients presented clinical manifestations of autoimmune disease. We conclude that elevated levels of AECA as well as anti-DNA and anti-CL autoantibodies are frequent in hyperprolactinemia. Our results further support the association of PRL and autoimmunity, and may point to a relationship between AECA-associated diseases and HRPL. The presence of autoantibodies in patients with HPRL might portend an increased risk for future development of autoimmune disease.
Lupus 1998
PMID:Anti-endothelial cell antibodies in the sera of hyperprolactinemic women. 973 19

It has become clear that beta2-glycoprotein I (beta2GPI) is the most common and best-characterised antigenic target for 'antiphospholipid' (aPL) autoantibodies. These antibodies preferentially bind beta2GPI that has been immobilised on anionic phospholipid membranes or certain synthetic surfaces. These surfaces appear to act by increasing antigen density to allow binding of intrinsically low-affinity anti-beta2GPI autoantibodies. Binding of beta2GPI in fluid phase is weak and requires high concentrations of beta2GPI. Our understanding of the pathophysiology of the 'Antiphospholipid' Syndrome (APS) has increased exponentially with the number of studies into the interactions of aPL antibodies and beta2GPI.
Lupus 1998
PMID:Beta2-glycoprotein I: target antigen for 'antiphospholipid' antibodies. Immunological and molecular aspects. 981 63

Apolipoprotein H (apoH; also known as beta2-glycoprotein I), is an essential cofactor for the binding of certain antiphospholipid antibodies (APA) to anionic phospholipid. The gene coding for apoH is polymorphic, with the occurrence of several common alleles in the general population. This genetically determined variation can effect the binding of apoH to anionic phospholipids and consequently the production of APA. Our group has identified two common mutations at codons 306 (Cys-->Gly) and 316 (Trp-->Ser) in the fifth domain of apoH which affect the binding of apoH to anionic phospholipids (phosphatidylserine or cardiolipin). ApoH from serum samples homozygous for each of these mutations or compound heterozygotes for both mutations showed no binding with anionic phospholipids on ELISA. In vitro mutagenesis and transient expression of these mutations in COS-1 cells followed by cardiolipin binding studies confirmed that Gly306 and Ser316 are causative mutations. Our data indicate that the fifth domain of apoH is essential for anionic phospholipid binding and genetically determined variation in this domain can affect the production of apoH-dependent APA.
Lupus 1998
PMID:Genetics of apolipoprotein H (beta2-glycoprotein I) and anionic phospholipid binding. 981 64

Anticardiolipin antibodies (aCL) found in sera from patients with antiphospholipid syndrome recognize a cryptic epitope that appears on the beta2-glycoprotein I (beta2-GPI) molecule when beta2-GPI interacts with a lipid membrane composed of negatively charged phospholipid or when beta2-GPI is adsorbed on a polyoxygenated polystyrene plate. A homology based model of beta2-GPI was constructed based on the NMR coordinates of sushi domains of human factor H. The conformation was like a cylinder consisting of five domains, its IV and V domains being glued by electrostatic interaction. We used phage-displayed random peptide libraries to search the epitopes of human aCL. Structures similar to consensus sequences selected by a biopanning method was found on domain IV of beta2-GPI.
Lupus 1998
PMID:Epitopes on beta2-GPI recognized by anticardiolipin antibodies. 981 65

Lupus anticoagulant antibodies form a heterogeneous group of antiphospholipid antibodies with rather poorly defined antigens. The role that phospholipid-binding proteins play in lupus anticoagulant antibody activity is a subject of current investigation. Several candidate proteins have been proposed, including beta2-glycoprotein I (beta2GPI), prothrombin, and annexin V. As beta2GPI-dependent lupus anticoagulants will be reviewed elsewhere in this issue, this paper will focus on the involvement of prothrombin and annexin V in lupus anticoagulant activity. Evidence for a role for these proteins in the reactivity and induction of lupus anticoagulant antibodies will be discussed, as well as an apparent requirement for both phospholipid and phospholipid-binding protein. The data presented here suggest that some lupus anticoagulant antibodies recognize and may be induced by complexes of phospholipid and phospholipid-binding proteins, in particular, phospholipid and prothrombin or annexin V.
Lupus 1998
PMID:Lupus anticoagulant antibodies: recognition of phospholipid-binding protein complexes. 981 68

Prothrombin is a common antigenic target of antiphospholipid antibodies, since anti-prothrombin antibodies are detected in about 50-90% of the patients. To allow proper immune recognition, prothrombin must be adsorbed on suitable anionic surfaces. The epitope(s) have not yet been identified: the majority of anti-prothrombin antibodies appear to be of poly- or oligoclonal nature. Anti-prothrombin antibodies, either alone or in combination with anti-beta2-glycoprotein I antibodies, are responsible for the lupus anticoagulant activity of about 75% of the cases of phospholipid-dependent inhibitors of coagulation. The two antibodies may be discriminated by means of specific coagulation profiles generated by the comparison of the ratio of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): the KCT profile, which mainly reflects the presence of anti-prothrombin antibodies and the dRVVT profile, which is mostly associated with anti-beta2-glycoprotein I antibodies. This distinction, although somewhat artificial, may be clinically useful, since the KCT profile identifies patients at low risk to develop thrombosis. Similarly, most of the studies that measured anti-prothrombin antibodies by ELISA failed to find a significant association with thrombosis. In conclusion, the clinical relevance of these antibodies has not yet been established.
Lupus 1998
PMID:Prothrombin as cofactor for antiphospholipids. 981 70

The clinical associations of antiphospholipid antibodies (aPL) are well recognized but the mechanism(s) causing the production of these antibodies are not yet known. We demonstrated the induction of pathogenic aPL antibodies that caused intrauterine fetal death and transverse myelopathy due to spinal cord infarction in mice by immunization with foreign beta2GPI. We also induced aPL and anti-beta2-GPI in mice by immunization with PL-binding viral peptides and hypothesized that in APS patients, aPL may be induced by beta2GPI-like-PL-binding products of common human bacteria and viruses.
Lupus 1998
PMID:Origin of antiphospholipid antibodies: induction of aPL by viral peptides. 981 74


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