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 - Funding Information:
The APS ACTION Registry was created using REDCap provided by the Clinical and Translational Science Center at Weill Cornell Medical College (CTSC grant UL1 TR000457).We are thankful to all patients included in the APS ACTION Registry. Consumables for aPL testing by Quanta Flash were kindly donated by Werfen. Neither Werfen nor any of their employees had any involvement in the design, execution, data analysis, or conclusions in this study. Open Access Funding provided by Universita degli Studi di Milano within the CRUI-CARE Agreement.
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 -