Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome☆

Abstract Introduction Antibodies directed against domain 1 of β2 glycoprotein 1 (aβ2GP1-Dm1) have been involved in the immunopathogenesis of antiphospholipid syndrome (APS). However, the clinical relevance of aβ2GP1-Dm1 in thrombotic APS has not yet been fully explored. Objectives To determine the frequency of aβ2GP1-Dm1 in a cohort of patients with thrombotic APS, and to evaluate whether testing for aβ2GP1-Dm1 could have a clinical impact upon the risk assessment of the disease. Methods Patients were tested for aβ2GP1-Dm1 antibodies by chemiluminescence (BioFlash/AcuStar®, ES). The presence of aβ2GP1-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 aβ2GP1 antibodies and 40% of them were positive for aβ2GP1-Dm1. Levels of aβ2GP1-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, aβ2GP1-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 aβ2GP1-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, aβ2GP1-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 aβ2GP1-Dm1 antibodies may be useful for improving APS risk assessment.