Antibodies to Domain I of β 2Glycoprotein I are in close relation to patients risk categories in Antiphospholipid Syndrome (APS)

Abstract

Introduction Antiphospholipid Syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Antibodies involved in these disorders are mainly those directed against β 2-Glycoprotein I (β 2GPI) with the major epitope apparently located on discontinuous antigen with several parts of Domain I (DmI) involved. The relation between anti-DmI antibodies and patients’ risk categories is unknown. Materials and Methods The synthetic full-length and correctly-folded DmI (1–64) to set up a competitive inhibition enzyme-linked immunoadsorbent assays (ELISA) was used. Plasma of 22 patients with APS and triple positivity [Lupus Anticoagulant positive (LAC+), IgG anti-cardiolipin positive (aCL+), IgG anti-β 2GPI positive (a β 2GPI +)], 15 with double positivity (IgG aCL+, IgG aβ 2GPI+), 9 with single positivity (IgG aβ 2GPI+) and 20 controls were evaluated. Results Median of percentage inhibition was 25.5% [interquartile range (IQR)17.2-33.0] in triple positive patients. Significantly lower inhibition was observed in patients with double positivity, median inhibition 5.0% (IQR 0.0-27.0) and in patients with single positivity median inhibition was 2.0% (IQR 0.5-8.0) (p < 0.0001). No inhibition was detected in control subjects or using β 2GPI peptides (40–52 and 57–70), or when antithrombin, an insignificant control protein was used. Conclusions High risk patients with APS and triple laboratory positivity as compared with double and single positivity patients have significantly higher titre of anti-DmI antibodies as evaluated by an inhibition test.