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 beta(2)-glycoprotein I (anti-beta(2)GPI) and domain 1 (anti-D1), to identify predictors of variations in anti-beta(2)GPI 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-beta(2)GPI 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-beta(2)GPI 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-beta(2)GPI 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-beta(2)GPI titers, respectively. Incident vascular events were associated with 1.9-fold and 2.1-fold increases in anti-D1 and anti-beta(2)GPI titers, respectively. Anti-D1 and anti-beta(2)GPI 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-beta(2)GPI 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-beta(2)GPI titer fluctuations over time. Both anti-D1 and anti-beta(2)GPI titers decreased around the time of thrombosis, with potential clinical relevance.

Automated summary

The study aims to evaluate the antibodies titers against beta(2)-glycoprotein I (anti-beta(2)GPI) and domain 1 (anti-D1) in a longitudinally manner. The results show that treatment with hydroxychloroquine (HCQ) is associated with a decrease in antibody titers, while incident vascular events are associated with an increase in antibody titers. The titers of antibodies are lower at the time of thrombosis. This study is of great importance in understanding the fluctuations in antibody titers and their relationship with thrombosis.