Anti β2 glycoprotein I antibodies: detection and association with thrombosis

Abstract

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.

High prevalence of anti‐prothrombin antibody in patients with deep vein thrombosis

“…Since only a few patients with thrombosis were positive for anti-b 2 GP1 IgM, this antibody may be low risk factor for thrombosis. In this regard, previous studies [25,26] reported the detection of IgG, and indicated that the presence of IgM anti-b 2 GP1 correlated significantly with a history of thrombosis. In particular, Guerin et al [25] used both anti-b 2 GP1 and conventional aCL assays and found that anti-b 2 GP1 IgG assays improved the diagnostic specificity relative to the conventional aCL assays.…”

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β2‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2‐Glycoprotein I and Induce Endothelial Activation

“…In addition, anti-P,GPI antibodies have been found in patients with APS (15)(16)(17)(18)(19)(20)(21). It is unclear, however, whether the antibodies recognize the proteins themselves, the PL-protein complex, or neo-or cryptic antigens eventually expressed as a result of the interaction (20,21).…”

“…In addition, antibodies reacting directly with p,GPI have been found. Both types of antibodies are thought to play a leading role in the pathogenesis of A P S since they closely correlate with the appearance of the typical clinical manifestations (15)(16)(17)(18)(19). Whether aPL-positive sera recognize epitopes displayed by P,GPI itself or whether the epitope consists of both P,GPI and cardiolipin (CL) is still open to discussion (20,21).…”

Risk of arterial thrombosis in patients with anticardiolipin antibodies and lupus anticoagulant

“…It is well known that the existence of aCL and/or LA is frequently found in the plasma of patients with systemic lupus erythematosus (SLE), and that these patients suffer from arterial or venous thrombosis (Lechner, 1987;Galli et al, 1990;Harris et al, 1983;Hughes et al, 1986;Hughes, 1993). Recently b2-glycoprotein I (b2-GP I) McNeil et al, 1990;Koike & Matsuura, 1991;Keeling et al, 1992;Matsuura et al, 1994) and prothrombin (Bevers et al, 1991;Oosting et al, 1993) were reported to be important epitopes recognized by these antiphospholipid antibodies, and the presence of anit-b2-GP I-IgG has been associated with a venous thromboembolism (Martinuzzo et al, 1995). However, the mechanisms involved in the development of thrombosis and other complications are not completely elucidated.…”