Anti-Domain I beta(2)-Glycoprotein I Antibodies and Activated Protein C Resistance Predict Thrombosis in Antiphospholipid Syndrome: TAC(I)T Study

Stephane Zuily, Bas de Laat, Francis Guillemin, Hilde Kelchtermans, Nadine Magy-Bertrand, Helene Desmurs-Clavel, Marc Lambert, Vincent Poindron, Emmanuel de Maistre, Virginie Dufrost, Jessie Risse, Zakera Shums, Gary L. Norman, Philip G. de Groot, Patrick Lacolley, Thomas Lecompte, Veronique Regnault, Denis Wahl*, TAC(I)T study group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

Background: Antibodies binding to domain I of beta(2)-glycoprotein I (aDI) and activated protein C (APC) resistance are associated with an increased risk of thrombosis in cross-sectional studies. The objective of this study was to assess their predictive value for future thromboembolic events in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome.

Methods: This prospective multicenter cohort study included consecutive patients with aPL or systemic lupus erythematosus. We followed 137 patients (43.5 +/- 15.4 year old; 107 women) for a mean duration of 43.1 +/- 20.7 months.

Results: We detected aDI IgG antibodies by ELISA in 21 patients. An APC sensitivity ratio (APCsr) was determined using a thrombin generation-based test. The APCsr was higher in patients with anti-domain I antibodies demonstrating APC resistance (0.75 +/- 0.13 vs 0.48 +/- 0.20, P <0.0001). In univariate analysis, the hazard ratio (HR) for thrombosis over time was higher in patients with aDI IgG (3.31 [95% CI, 1.15-9.52]; P = 0.03) and patients with higher APC resistance (APCsr >95th percentile; HR, 6.07 [95% CI, 1.69-21.87]; P = 0.006). A sensitivity analysis showed an increased risk of higher aDI IgG levels up to HR 5.61 (95% CI, 1.93-16.31; P = 0.01). In multivariate analysis, aDI IgG (HR, 3.90 [95% CI, 1.33-11.46]; P = 0.01) and APC resistance (HR, 4.98 [95% CI, 1.36-18.28]; P = 0.02) remained significant predictors of thrombosis over time.

Conclusions: Our study shows that novel tests for antibodies recognizing domain I of beta(2)-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.

Original languageEnglish
Pages (from-to)1242-1252
Number of pages11
JournalJournal of Applied Laboratory Medicine
Volume5
Issue number6
DOIs
Publication statusPublished - Nov 2020

Keywords

  • CLASSIFICATION CRITERIA
  • LUPUS ANTICOAGULANTS
  • REVISED CRITERIA
  • 1ST EPISODE
  • RISK
  • GENERATION
  • STANDARDIZATION
  • AUTOANTIBODIES
  • ASSOCIATION
  • RECOGNIZE

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