Fluctuation of Anti-Domain 1 and Anti-Β2 Glycoprotein I Antibody Titers Over Time in Patients with Persistently Positive Antiphospholipid Antibodies

OBJECTIVE: This work aims at evaluating longitudinally titers of antibodies against β2-glycoprotein I (β2GPI) and domain 1 (anti-D1), identifying predictors of the variation of anti-D1 and anti-β2GPI antibody titers and clarifying whether antibody titer fluctuations predict thrombosis in a large international cohort of patients persistently positive for antiphospholipid antibodies (aPL), the "APS ACTION Registry". METHODS: Patients with available blood samples from at least 4 time points were included. Anti-β2GPI and anti-D1 IgG were tested by chemiluminescence (BioFlash, INOVA Diagnostics). RESULTS: In a cohort of 230 patients, anti-D1 and anti-β2GPI titers decreased significantly over time (p<0.0001 and p=0.010, respectively). After adjustment for age, gender, and number of positive aPL tests, the fluctuation of anti-D1 and anti-β2GPI titers was associated with treatment with hydroxychloroquine (HCQ) at each time-point. Treatment with HCQ, but not immunosuppressors, was associated with 1.3-fold and 1.4-fold decrease in anti-D1 and anti-β2GPI titers, respectively. Incident vascular events were associated with 1.9-fold and 2.1-fold increase of anti-D1 and anti-β2GPI titers, respectively. Anti-D1 and anti-β2GPI titers at the time of thrombosis were lower compared to the other time-points: 1.6-fold decrease in anti-D1 titers and 2-fold decrease in anti-β2GPI titers conferred an OR for incident thrombosis of 6.0 (95%CI 0.62-59.3) and 9.4 (95%CI 1.1-80.2), respectively. CONCLUSIONS: Treatment with HCQ and incident vascular events significant predicted anti-D1 and anti-β2GPI titer fluctuation over time. Both anti-D1 and anti-β2GPI titers drop around the time of thrombosis, with potential clinical relevance. This article is protected by copyright. All rights reserved