anti-beta2GPI Antibodies Research Articles

Phospholipid-Dependent Anti-.BETA.2-Glycoprotein I (.BETA.2-GPI) Antibodies and Antiphospholipid Syndrome.

A portion of anticardiolipin antibodies is defined as phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies and recognizes the conformationally altered beta 2 GPI which interacts with anionic phospholipids. We studied the clinical significance of IgG phospholipid-dependent anti-beta 2-GPI antibodies in patients with antiphospholipid syndrome (APS). The subjects consisted of 60 APS patients. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected by ELISA in 32 of the 60 patients (53%). Significantly higher incidences of prolonged APTT and lupus anticoagulants were found in patients with these anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash, serositis, LE cell preparation and anti-Sm antibodies were found in patients with these anti-beta 2-GPI antibodies. It was found that 88% of the patients with these anti-beta 2-GPI antibodies satisfied less than five of the revised criteria items for the classification of SLE. These findings indicate the clinical characteristics of APS patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies.

Species Specificity of Anti-β2 Glycoprotein I Autoantibodies and Its Relevance to Anticardiolipin Antibody Quantitation

Some patients suspected of having antiphospholipid antibody syndrome (APS) were found to be positive for anti-beta 2 glycoprotein I (beta 2GPI) antibodies despite negative results for antibodies to cardiolipin (ACA). Since the major source of beta 2GPI in the ACA assay is animal (usually bovine) serum, we studied the influence on ACA quantitation of the species specificity of anti-beta 2GPI antibodies from patients with various autoimmune disorders, mostly systemic lupus erythematosus and primary APS. Ninety-seven sera were selected based on IgG (n = 76) or IgM (n = 64) positivity by ELISA using gamma-irradiated plates coated with human or bovine purified beta 2GPI. A higher proportion of IgM (43.7%) than IgG (7.9%) reacted to human, but not bovine, beta 2GPI. Furthermore, from the samples reactive to both proteins, the ratio of antibody level against bovine to that against human beta 2GPI was 1.08 +/- 0.58 for IgG and 0.58 +/- 0.3 for IgM (p < 10(-5)). IgG and IgM ACA were detected in 78 and 40 sera, respectively; concordance between the two ELISAs for ACA and anti-beta 2GPI antibodies was 94% for IgG and 75% for IgM. Out of 28 IgM showing recognition restricted to human beta 2GPI, 21 were missed by the ACA assay, possibly because of lower concentrations of beta 2GPI in those patients' sera. The antibody reactivity pattern towards human and bovine beta 2GPI of individual sera showed no variation with time and was related to the relative antibody avidity for each protein. A murine anti-human beta 2GPI monoclonal antibody, 9G1, that cross-reacts with bovine beta 2GPI, competed to a large extent with the patients' anti-beta 2GPI antibody binding sites whatever isotype involved or protein recognized. Therefore, anti-beta 2GPI antibodies of IgM isotype display a marked preference for human compared to bovine beta 2GPI responsible for frequent inconsistencies in the ACA assay.

Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in systemic lupus erythematosus.

We investigated the clinical significance of IgG phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-beta 2-GPI antibodies by ELISA. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies show an unique form of SLE.

Anti beta 2 glycoprotein I antibodies: detection and association with thrombosis.

It has been demonstrated that antiphospholipid antibodies (aPL) recognize epitopes formed by anionic phospholipids and protein cofactors. beta 2 glycoprotein I (beta 2GPI) is accepted as the cofactor of anticardiolipin antibodies (aCL). In the present study we explored the presence and clinical associations of anti beta 2GPI antibodies of IgG isotype (a beta 2GPI-IgG), measured by ELISA. We studied sera from 169 patients with aCL and/or lupus anticoagulant (LA), including 52 patients with systemic lupus erythematosus and 49 with primary antiphospholipid syndrome (PAPS). We found 31.9% positive sera for a beta 2GPI-IgG in the whole population and 48.6% in the aCL-IgG(+) group. There was a good correlation between the titre of aCL-IgG and the optical density for a beta 2GPI-IgG (r = 0.69, P < 0.01). The presence of a beta 2GPI-IgG was associated with the presence of aCL-IgG (P < 0.0001) and LA (P < 0.0005). However, none of 23 LA (+) patients without aCL had a beta 2GPI-IgG. We found a statistically significant association between the presence of a beta 2GPI-IgG and a history of venous thromboembolism (VTE) in our patients (P < 0.005). This association was observed in PAPS (P < 0.05) but not in secondary antiphospholipid syndrome (SAPS). Our study confirms that some aPL(+) sera react with beta 2GPI in special experimental conditions. In addition, the presence of these antibodies is associated with a history of VTE.

A new player in the antiphospholipid syndrome: the beta 2 glycoprotein I cofactor.

The study of antiphospholipid (aPL) antibodies has been greatly developed in recent years and conclusive evidence now exists concerning the correlation between aPL and clinical signs such as thrombosis, thrombocytopenia, abortion, and fetal loss. Several hypotheses have been put forward concerning the pathogenic mechanism of aPL, but none has received final confirmation from experimental data. Many studies have been devoted to characterizing the antigens recognized by the different aPL autoantibodies and to a cofactor involved in the binding of autoantibodies and phospholipids; this cofactor has been identified as an apolipoprotein, the beta 2 glycoprotein I (beta 2GPI) or APO-H. Direct evidence now exists which suggests that both the beta 2GPI and the phospholipid comprise the epitope to which aPL are directed. On the other hand anti-beta 2GPI antibodies have been identified in sera of patients suffering from SLE and primary Antiphospholipid Syndrome. beta 2GPI is normally present in human plasma/serum and possesses numerous inhibitory functions in multiple coagulation pathways. The amino acid sequence of beta 2GPI has been identified and found to consist of five repeating units that belong to the complement control protein (CCP) superfamily. This development of knowledge related to aPL has followed three steps respectively: 1. the standardization of the techniques of detection: 2. identification of the clinical signs related to the autoantibodies: and finally 3. the discovery of a new player, the beta 2GPI cofactor.