Antiphospholipid syndrome: antibodies to Domain 1 of β2-glycoprotein 1 correctly classify patients at risk

Abstract

Background: Determination of lupus anticoagulant (LA), anticardiolipin (aCL) and β2-Glycoprotein 1 (aβ2GP1) antibodies is mandatory to classify patients with antiphospholipid syndrome (APS) into risk categories.

Objectives: To measure relevant antibodies, considered to be those of the IgG isotype directed towards β2GP1 and particularly those directed to Domain 1 (Dm1) of the molecule.

Patients/methods: In this cross-sectional study we measured IgG aβ2GP1-Dm1 by a chemiluminescent immunoassay in a group of individuals initially positive for IgG aβ2GP1 and classified as triple (LAC+, IgG aCL+, IgG aβ2GP1+, n = 32), double (LAC-, IgG aCL+, IgG aβ2GP1+, n = 23) or single positive (LA-, IgG aCL-, IgG aβ2GP1+, n = 10).

Results and conclusion: Geometric mean and standard deviation expressed as chemiluminescent units (CU) in triple, double and single positive groups were 273.0 ± 6.2, 18.2 ± 9.6 and 4.4 ± 2.2, respectively. The geometric mean obtained in 40 healthy subjects was 2.0 ± 2.0. Mean CU values were significantly different among groups and with respect to values found in 40 healthy subjects (P < 0.0001). Positive values of IgG aβ2GP1-Dm1 (above 14.2 CU) were found in 45 individuals while 20 individuals (20/65 = 30.8%) positive for IgG aβ2GP1 were negative for IgG aβ2GPI-Dm1. There was a significant association between positive IgG aβ2GP1-Dm1 and thromboembolic events (P = 0.001). Positive and negative values of IgG aβ2GP1-Dm1 were consistently confirmed after 12 weeks, with only three low positive values being negative after 12 weeks. In conclusion, IgG aβ2GP1-Dm1 seems a robust and reproducible test that in association with the classic tests may be useful in clinical practice in identifying individuals at high risk of developing thromboembolic events.

Keywords: antibodies; antiphospholipid syndrome; epitopes; glycoproteins; thrombosis.