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 antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE)) and a hospital-based (87 patients with SLE and 53 with other connective tissue diseases) were investigated for APA and associated clinical manifestations. Anticardiolipin antibodies (ACA) of IgG and IgM classes were found in 13 and 38% of the population-based patients and in 29 and 58% of the hospital-based patients, respectively. The corresponding figures for antibodies against beta2-glycoprotein I (anti-beta2GPI) were 15 and 10% in the population-based patients and 14 and 8% in the hospital-based cohort. Anti-beta2GPI antibodies were always found in association with the corresponding immunoglobulin class of ACA. In both cohorts anti-beta2GPI of the IgG class were associated with arterial/venous occlusion, a result concordant with other studies. A novel finding in both cohorts, however, was an association between thrombocytopenia and IgM anti-beta2GPI.
Lupus 2001
PMID:Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia. 1153 Sep 94

The antiphospholipid syndrome (APS) is a thrombotic disorder leading to spontaneous abortions, venous thromboses, myocardial infarctions and strokes. Although the syndrome is associated with characteristic autoantibodies, these tests have poor predictive value for thrombosis. The aim of the study was to determine whether the combined presence of two types of antiphospholipid antibodies can be associated with a high-risk subset of thrombosis-prone patients. One hundred and thirty-four sera from a lupus clinic were tested for antibodies to beta2-glycoprotein I (beta2GPI), protein S and prothrombin. In a group of 29 patients for whom plasma was available, free (functional) protein S levels were also measured. Autoantibodies to beta2GPI and protein S are associated with each other. Dual reactivity to beta2GPI and protein S correlates with increased history of thrombotic events (69% of doubly reactive patients) when compared to either type of autoantibody alone (37% of patients with only anti-beta2GPI and 38% with only anti-protein S, P=0.04 and P=0.01, respectively) or neither reactivity (37%). Among 29 patients tested for free (functional, anticoagulant) protein S levels, the lowest levels were found in patients with antibodies to beta2GPI and/or protein S, and all four patients with a history of thrombosis had below-normal free protein S levels. These associations were not found with antiprothrombin antibodies. In conclusion dual autoantibodies to beta2GPI and protein S are associated with increased history of thrombosis in the antiphospholipid syndrome.
Lupus 2002
PMID:Dual antibody reactivity to beta2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome. 1204 84

We studied 99 patients with systemic autoimmune disease (5 males, 94 women; mean age 37 year, range 16-72): 28 Primary Antiphospholipid Syndrome, 67 Systemic lupus Erythematosus, 1 Mixed Connective Tissue Disease, 2 Undifferentiated Connective Tissue Disease and 1 Discoid Lupus. Based on the observation that native PT shows conformational changes in presence of Ca++ ions and discloses new epitopes available for binding with phospholipids, we performed 3 different methods for the detection of aPT in presence and absence of Ca++, finding a different incidence of specific autoantibodies, associated with clinical features of APS (aPT in presence of Ca++) or non associated (aPT in absence of Ca++). The presence of aPT was significantly associated also with the presence of Lupus Anticoagulant (LAC). The detection of aPT (in presence of Ca++) significantly enhances diagnostic sensibility of APS allowing the identification of a subset of patients (6/99) with clinical features of APS, but with negative LAC, aCL and a beta2-GPI; in fact (limited to thrombotic episodes) the sensibility rises from 56.2% with one test (LAC) to 81.1% with the application of LAC, aCL, a(beta)2GPI and aPT.
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PMID:[Role of anti-prothrombin in antiphospholipid syndrome]. 1240 33

Antiphospholipid antibodies (aPL) may induce acquired activated protein C resistance (acquired APCR). The role of acquired APCR in patients with systemic lupus erythematosus (SLE) is not well known. To evaluate the prevalence of acquired APCR and its association with clinical manifestations we studied 103 consecutive SLE patients and 103 matched controls. APCR in the undiluted test and after dilution in factor V deficient plasma, factor V Leiden, protein C and S, lupus anticoagulant, and anti-cardiolipin, anti-beta2-glycoprotein I and anti-prothrombin antibodies were determined. Factor V Leiden was found in 4% in both patients and controls. The prevalence of acquired APCR was 22% for the undiluted assay and 17% in the diluted test. In SLE patients, acquired APCR was associated with aPL (39 vs 13% in undiluted assay, P = 0.007; and 33 vs 7% in the diluted test, P = 0.001). Arterial thromboses were found in 24% of patients with acquired APCR and in 6% of patients without (P = 0.04). However, no relationship was found with venous thrombosis. Acquired APCR was also associated with pregnancy losses: miscarriages in 70% of women with acquired APCR vs 32% in those without (P=0.03). Thus, in SLE patients acquired APCR seems to be associated with increased prevalence of arterial thrombosis and pregnancy losses.
Lupus 2002
PMID:Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus. 1247 3

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.
Lupus 2002
PMID:Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies. 1247 4

Autoantibodies binding beta2-glycoprotein I (B2GPI) are an important finding in the antiphospholipid syndrome. While antibodies from mice or rabbits immunized with B2GPI readily bind B2GPI coated on a polystyrene microwell plate, anti-B2GPI autoantibodies only do so when using a modified microwell plate with a negatively charged surface. This study demonstrates that, for the detection of anti-B2GPI autoantibodies in an ELISA using modified plates, an antigen coating concentration threshold exists, such that minimal or no binding occurs below a certain coating concentration of antigen, even though antigen is easily demonstrable on the plate. This is consistent with the hypothesis that autoantibodies require divalent binding to B2GPI for detection, as sufficient antigen density for two protein molecules to be sufficiently close to enable divalent binding would only be expected to occur at higher coating concentrations. Several mutant forms of B2GPI developed for epitope determination experiments are shown to have decreased binding to microtitre plates compared to wild-type. If wild-type and mutants are assayed for antibody binding near the threshold a significant diminution in binding to mutants occurs that is the result of inadequate binding to the plate, but could be misinterpreted as the result of interruption of an epitope by the mutation.
Lupus 2003
PMID:Anti-beta2-glycoprotein I autoantibodies require an antigen density threshold, consistent with divalent binding. 1258 25

Antibodies to factor XII (FXIIabs) have been demonstrated in some patients with the anti-phospholipid syndrome (APS). The presence of these antibodies were shown to lead to statistically significantly reduced levels of FXII (p = 0.02). In an extension to this study forty female patients with either primary APS (n = 26) or systemic lupus erythematosus (APS positive) (n = 14) were investigated for levels of factor XII, the presence of lupus anticoagulant and antibodies to cardiolipin, beta 2-glycoprotein I and factor XII. Twenty one of the forty patients had a history of foetal loss (> 2, mean = 2.6). Lupus anticoagulant positivity showed a weak association with foetal loss (odds ratio = 1.1). While there was no association between the presence of antibodies to cardiolipin or beta 2-glycoprotein I with foetal loss, antibodies to factor XII showed a strong and statistically significant association (odds ratio = 5.4, p = 0.025).
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PMID:Antibodies to factor XII: a possible predictive marker for recurrent foetal loss. 1263 2

Lupus anticoagulants (LAC) are a heterogeneous group of autoantibodies that prolong phospholipid-dependent clotting assays. The autoantibodies that cause LAC activity are predominantly directed against beta2-glycoprotein I (beta2GPI) or prothrombin. In the present study, we describe a method to differentiate between LAC caused by antibodies directed against beta2GPI or prothrombin. Monoclonal antibodies, affinity purified patient antibodies, and selected patient samples were used to show that in an aPTT-based clotting assay (PTT-LA; Diagnostica Stago), the use of cardiolipin vesicles in the neutralization procedure discriminates between beta2GPI- or prothrombin-dependent LAC activities. Addition of cardiolipin vesicles shortened the prolonged clotting time caused by anti-beta2GPI antibodies with LAC activity, whereas this procedure further prolonged clotting times caused by antiprothrombin antibodies with LAC activity. In contrast, addition of phosphatidylcholine/phosphatidylserine vesicles corrected prolonged clotting times caused by either anti-beta2GPI or antiprothrombin antibodies with LAC activity. The effects of cardiolipin (CL) on beta2GPI-induced LAC activity were specific for contact activation mediated clotting assays. Possible explanations for these findings are the relatively high affinity of beta2GPI for cardiolipin, as determined by surface plasmon resonance analysis, and inhibition by anti-beta2GPI antibodies of the CL-induced prolongation of the PTT-LA.
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PMID:A simple method to discriminate between beta2-glycoprotein I- and prothrombin-dependent lupus anticoagulants. 1287 10

Detection of antiphospholipid (aPL) antibodies in bronchoalveolar lavage fluid (BALF) of patient with acute respiratory distress syndrome (ARDS) suggests involvement of autoimmune mechanisms in the pathogenesis of ARDS. We investigated whether aPL antibodies could be detected in the serum as well as BALF of patients with acute lung injury (ALI) and ARDS. IgG anticardiolipin, IgG anti-beta2-glycoprotein I, IgG antiphosphatidic acid and IgG antiphosphatidylserine antibodies were detected by ELISA in low titers within the normal range in the BALF and serum of nine patients with ALI and 17 patients with ARDS. However, one out of 27 patients investigated had high levels of aPL antibodies in both BALF and serum. This patient suffered from severe ARDS due to sepsis. The high aPL antibody levels in serum possibly triggered by sepsis were associated with high aPL antibody levels in BALF, which can be explained by high capillary-alveolar permeability. Computed tomography scan revealed widespread infarctions in brain, spleen and kidneys, and pulmonary thromboembolism, suggesting the diagnosis of catastrophic antiphospholipid syndrome.
Lupus 2003
PMID:Prospective observational study of antiphospholipid antibodies in acute lung injury and acute respiratory distress syndrome: comparison with catastrophic antiphospholipid syndrome. 1287 48

Though many neurological deficits have been described in the antiphospholipid syndrome (APS), only stroke is well established and accepted as a diagnostic criterion in this disease. We review clinical data obtained from a large series of cases regarding stroke, dementia, epilepsy, chorea, migraine, white matter disease and behavioral changes in APS or linked to laboratory criteria such as antiphospholipid antibodies (aPL). The contribution of animal models to our understanding of these manifestations of APS is stressed, especially regarding the cognitive and behavioral aspects for which we have established model systems in the mouse. These models utilize immunization of mice with beta2-glycoprotein I, a central autoantigen in APS, which induces persistent high levels of aPL. These mice develop hyperactive behavior after a period of four to five months as well as deficits in learning and memory and are potentially valuable as a system in which to study the pathogenesis and treatment of cognitive and behavioral aspects of APS. Another model we have developed, in which IgG from APS patients induce depolarization of brain synaptoneurosomes, may serve as a model for the pathogenesis of epilepsy in APS.
Lupus 2003
PMID:CNS dysfunction in the antiphospholipid syndrome. 1471 9


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