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

Abstract

ObjectiveThe 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.MethodsPatients 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).ResultsAmong 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.ConclusionTreatment 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.