TY - JOUR
T1 - Fluctuation of Anti–Domain 1 and Anti–β2-Glycoprotein I Antibody Titers Over Time in Patients With Persistently Positive Antiphospholipid Antibodies
AU - Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION)
AU - Chighizola, Cecilia B.
AU - Pregnolato, Francesca
AU - Andrade, Danieli
AU - Tektonidou, Maria
AU - Pengo, Vittorio
AU - Ruiz-Irastorza, Guillermo
AU - Belmont, H. Michael
AU - Gerosa, Maria
AU - Fortin, Paul
AU - Branch, D. Ware
AU - Andreoli, Laura
AU - Petri, Michelle A.
AU - Cervera, Ricard
AU - Knight, Jason S.
AU - Willis, Rohan
AU - Efthymiou, Maria
AU - Cohen, Hannah
AU - Erkan, Doruk
AU - Bertolaccini, Maria Laura
AU - Pons-Estel, Guillermo
AU - Giannakopoulos, Bill
AU - Krilis, Steve
AU - de Jesus, Guilherme
AU - Levy, Roger
AU - Signorelli, Flavio
AU - Andrade, Danieli
AU - Balbi, Gustavo
AU - Clarke, Ann E.
AU - Skeith, Leslie
AU - Fortin, Paul R.
AU - Ji, Lanlan
AU - Zhang, Zhouli
AU - Yang, Chengde
AU - Shi, Hui
AU - Zuily, Stephane
AU - Wahl, Denis
AU - Tektonidou, Maria G.
AU - Nalli, Cecilia
AU - Andreoli, Laura
AU - Tincani, Angela
AU - Chighizola, Cecilia B.
AU - Gerosa, Maria
AU - Meroni, Pier Luigi
AU - Pengo, Vittorio
AU - Cheng, Chunyan
AU - Pazzola, Giulia
AU - Sciascia, Savino
AU - Foddai, Silvia
AU - Radin, Massimo
AU - Gonzalez, Emilio
N1 - Publisher Copyright:
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
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U2 - 10.1002/art.42459
DO - 10.1002/art.42459
M3 - Article
C2 - 36704930
AN - SCOPUS:85152452844
SN - 2326-5191
VL - 75
SP - 984
EP - 995
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 6
ER -