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

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(2)GPI) 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(2)GPI positive (a β(2)GPI +)], 15 with double positivity (IgG aCL+, IgG aβ(2)GPI+), 9 with single positivity (IgG aβ(2)GPI+) 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(2)GPI 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.