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)

Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid syndrome (APS) were found by many investigators, but their results appeared contraversional. We studied clinical significance of antibodies to beta 2-glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL) and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI, respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS development as a whole, its separate clinical symptoms (venous and arterial thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more frequently in the sera positive by LA and aCL. It is interesting that we discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is clinically important for upgrading diagnosis of APS.
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PMID:[Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new laboratory marker of antiphospholipid syndrome]. 957 46

It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via beta2-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of beta2-GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of beta2-GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r = 0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, beta2-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of beta2-GPI to protein C and its phospholipid dependency were investigated. Beta2-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated in the presence of cardiolipin and beta2-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and beta2-GPI, whereas they did not in the absence of either beta2-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and beta2-GPI, leading to protein C dysfunction.
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PMID:Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system. 964 98

Sera from 20 patients with antiphospholipid syndrome (APS), primary or secondary to systemic lupus erythematosus (SLE), or with SLE, were assayed by immunoblot analysis for anti-beta2-glycoprotein I antibodies (abeta2-GPI), and by indirect immunofluorescence (IIF) technique for reactivity with astrocyte and neuron cell lines and with histological sections of human brain biopsies and monkey cerebellum. Six sera from healthy donors were studied as a control. Eleven out of the 20 patient sera contained abeta2-GPI and were immunoreactive with astrocytes and neurons, both in culture and in the histological sections, and with the endotheliocytes of the microvessels present in the histological sections. Cell localization and the pattern of immune reaction were similar to those obtained with a monoclonal antibody abeta2-GPI. Eight of the remaining patient sera, found abeta2-GPI-, did not react with the nervous substrates (and the control sera), while one exhibited immunoreactivity analogous to the abeta2-GPI+ sera. The interference of anticardiolipin antibodies (aCL) in the immunoreactivity with the nervous substrates was excluded since aCL were present in all patient sera and no immune reaction was observed in the histological sections incubated with a monoclonal aCL. Therefore, the binding of abeta2-GPI from patients to cells of the central nervous system (CNS) occurs independently from aCL. This issue may be relevant to further evaluate the potential pathogenetic role of abeta2-GPI in the CNS damage of APS-like conditions.
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PMID:Serum anti-beta2-glycoprotein I antibodies from patients with antiphospholipid antibody syndrome bind central nervous system cells. 980 25

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.
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PMID:Anti-beta2-glycoprotein I antibodies. 981 83

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.
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PMID:Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease. 982 43

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

The high affinity of human plasma beta2-glycoprotein I (beta(2)GPI), also known as apolipoprotein-H (ApoH), for negatively charged phospholipids determines its implication in a variety of physiological pathways, including blood coagulation and the immune response. beta(2)GPI is considered to be a cofactor for the binding of serum autoantibodies from antiphospholipid syndrome (APS) and correlated with thrombosis, lupus erythematosus and recurrent fetal loss. We solved the beta(2)GPI structure from a crystal form with 84% solvent and present a model containing all 326 amino acid residues and four glycans. The structure reveals four complement control protein modules and a distinctly folding fifth C-terminal domain arranged like beads on a string to form an elongated J-shaped molecule. Domain V folds into a central beta-spiral of four antiparallel beta-sheets with two small helices and an extended C-terminal loop region. It carries a distinct positive charge and the sequence motif CKNKEKKC close to the hydrophobic loop composed of residues LAFW (313-316), resulting in an excellent counterpart for interactions with negatively charged amphiphilic substances. The beta(2)GPI structure reveals potential autoantibody-binding sites and supports mutagenesis studies where Trp316 and CKNKEKKC have been found to be essential for the phospholipid-binding capacity of beta(2)GPI.
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PMID:Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. 1056 35

We examined the role of autoantibodies to beta2-GPI and prothrombin (PT) in the inhibition of annexin V binding to cardiolipin (CL) and the association with clinical manifestations of the anti-phospholipid syndrome (APS). Plasma samples from 59 patients with anti-phospholipid (aPL) antibodies were studied. Affinity purification of total IgG and IgG anti-ss2-GPI antibodies was performed using staphylococcal protein A and phospholipid liposomes. Annexin V binding to CL was significantly inhibited by 31/59 (53%) aPL+ plasma samples. There was a significant association between annexin V inhibition and elevated levels of IgG anti-cardiolipin (aCL) (r = -0.62; P < 0.001), IgG anti-ss2-GPI (r = -0.67; P < 0. 001) and a weaker association with lupus anti-coagulant (r = -0.27; P = 0.05). There was no association with other isotypes of aCL and anti-ss2-GPI or with anti-PT of any isotype. In patients with clinical manifestations of the APS there were higher levels of IgG aCL (median (range) Z score): 10.0 (0-17.6) versus 5.0 (0-16.1); P = 0.03), IgG anti-ss2-GPI (4.5 (0-11.3) versus 0.9 (0-9.7); P = 0.02) and greater inhibition of annexin V binding to CL (-3.4 (-11.4-0.6) versus -1.1 (-10.8-1.2); P = 0.22). Odds ratios for the laboratory assays and the presence of clinical manifestations of the APS varied between 0.38 and 4.16, with the highest values for IgG aCL (4.16), IgG anti-ss2-GPI (3.28) and annexin V inhibition (2.85). Additional experiments with affinity-purified IgG antibodies indicated that inhibition of annexin V binding was dependent upon the concentration of ss2-GPI and anti-ss2-GPI antibodies. These results indicate that inhibition of annexin V binding to procoagulant phospholipid surfaces is dependent upon anti-ss2-GPI antibodies and suggest a role for annexin V in the pathogenesis of the APS.
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PMID:Anti-beta2-glycoprotein I (GPI) autoantibodies, annexin V binding and the anti-phospholipid syndrome. 1084 35

Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis and fetal loss. Two hundred eighty-nine patients with a history of recurrent spontaneous abortion were subjected to screening examinations for the etiology of these abortions. Endocrine abnormality (28.0%), uterine abnormality (10.4%), autoimmune diseases (1.4%), antiphospholipid antibody syndrome (4.5%), and balanced type chromosome translocation (4.2%) were found as underlying causes of recurrent abortions, and the remaining 55.0% of the 289 patients were classified as having an unexplained etiology. Congenital thrombophilia such as protein C (PC) deficiency, protein S (PS) deficiency, antithrombin deficiency, and factor V Leiden mutation was not frequently detected; only one patient had PS deficiency. A reduced factor XII activity was found at a frequency of 4.2%. The frequency of methylene tetrahydrofolate reductase gene C677T mutation in recurrent aborters (0.38) was the same as that found in a fertile control group. Although the prevalence of anti-beta2-glycoprotein I antibody (abeta2-GPI) syndrome was very low (1.7%), patients with a high titer of immunoglobulin G (IgG) class abeta2-GPI, despite anticoagulation therapy, experienced severe fetomaternal complications in subsequent pregnancies. The rate (13.8%) of positive tests for serum IgA class abeta2-GPI in patients with unexplained etiology was higher than that in the controls (0%) (P < .05). We conclude that congenital thrombophilia is rare in Japanese patients who had experienced consecutive spontaneous abortions.
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PMID:Recurrent pregnancy loss: etiology of thrombophilia. 1137 65

The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.
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PMID:Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies. 1247 4


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