Clinical implications of the detection of antibodies directed against domain 1 of ß2-glycoprotein 1 in thrombotic antiphospholipid syndrome.

ABSTRACT

INTRODUCTION: Antibodies directed against domain 1 of ß2 glycoprotein 1 (aß2GP1-Dm1) have been involved in the immunopathogenesis of antiphospholipid syndrome (APS). However, the clinical relevance of aß2GP1-Dm1 in thrombotic APS has not yet been fully explored. OBJECTIVES: To determine the frequency of aß2GP1-Dm1 in a cohort of patients with thrombotic APS, and to evaluate whether testing for aß2GP1-Dm1 could have a clinical impact upon the risk assessment of the disease. METHODS: Patients were tested for aß2GP1-Dm1 antibodies by chemiluminescence (BioFlash/AcuStar®, ES). The presence of aß2GP1-Dm1 was evaluated in different clinical presentations of the disease. RESULTS: Eight-four patients with a history of venous or arterial thrombosis were included. Forty-five (54%) patients had aß2GP1 antibodies and 40% of them were positive for aß2GP1-Dm1. Levels of aß2GP1-Dm1 were higher in patients with systemic autoimmune disease (AUC=0.665; 95% CI=0.544-0.786; P=0.01), positive antinuclear antibody (AUC=0.654; 95% CI=0.535-0.772; P=0.01), triple antiphospholipid antibody (aPL) positivity (AUC=0.680; 95% CI=0.534-0.825; P=0.02) and positive lupus anticoagulant (AUC=0.639; 95% CI=0.502-0.776; P=0.07). In this cohort, aß2GP1-Dm1 antibodies were not associated with the site of the first thrombosis (OR=0,62, 95% CI=0.20-1.94, P=0.42), thrombosis recurrence (OR=1.0, 95% CI=0.37-2.71, P=1.0) or pregnancy morbidity (OR=1.5, 95% CI=0.33-7.34, P=0.58). In multivariate analysis, positivity for aß2GP1-Dm1 antibodies was associated with the diagnosis of systemic autoimmune disease (OR=4.01, 95% CI=1.14-14.2; P=0.03) and triple aPL positivity (OR=3.59, 95% CI=0.87-14.85; P=0.07). CONCLUSIONS: In the present cohort of thrombotic-APS patients, aß2GP1-Dm1 antibodies were related to the diagnosis of systemic autoimmunity and complex serological profile of the disease, as triple aPL positivity and positive antinuclear antibody. Thus, our results suggest that testing for aß2GP1-Dm1 antibodies may be useful for improving APS risk assessment.