Fluctuation of Anti–Domain 1 and Anti–β₂-Glycoprotein I Antibody Titers Over Time in Patients With Persistently Positive Antiphospholipid Antibodies

Objective: The present study was undertaken to longitudinally evaluate titers of antibodies against β₂-glycoprotein I (anti-β₂GPI) and domain 1 (anti-D1), to identify predictors of variations in anti-β₂GPI and anti-D1 titers, and to clarify whether antibody titer fluctuations predict thrombosis in a large international cohort of patients who were persistently positive for antiphospholipid antibodies (aPL) in the APS ACTION Registry. Methods: Patients with available blood samples from at least 4 time points (at baseline [year 1] and at years 2–4 of follow-up) were included. Detection of anti-β₂GPI and anti-D1 IgG antibodies was performed using chemiluminescence (BIO-FLASH; INOVA Diagnostics). Results: Among 230 patients in the study cohort, anti-D1 and anti-β₂GPI titers decreased significantly over time (P < 0.0001 and P = 0.010, respectively). After adjustment for age, sex, and number of positive aPL tests, we found that the fluctuations in anti-D1 and anti-β₂GPI titer levels were associated with treatment with hydroxychloroquine (HCQ) at each time point. Treatment with HCQ, but not immunosuppressive agents, was associated with 1.3-fold and 1.4-fold decreases in anti-D1 and anti-β₂GPI titers, respectively. Incident vascular events were associated with 1.9-fold and 2.1-fold increases in anti-D1 and anti-β₂GPI titers, respectively. Anti-D1 and anti-β₂GPI titers at the time of thrombosis were lower compared to titers at other time points. A 1.6-fold decrease in anti-D1 titers and a 2-fold decrease in anti-β₂GPI titers conferred odds ratios for incident thrombosis of 6.0 (95% confidence interval [95% CI] 0.62–59.3) and 9.4 (95% CI 1.1–80.2), respectively. Conclusion: Treatment with HCQ and incident vascular events in aPL-positive patients predicted significant anti-D1 and anti-β₂GPI titer fluctuations over time. Both anti-D1 and anti-β₂GPI titers decreased around the time of thrombosis, with potential clinical relevance.