1. Anti-Domain I beta(2)-Glycoprotein I Antibodies and Activated Protein C Resistance Predict Thrombosis in Antiphospholipid Syndrome
- Author
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Patrick Lacolley, Véronique Regnault, Marc Lambert, Philip G. de Groot, Hilde Kelchtermans, Emmanuel de Maistre, Zakera Shums, Nadine Magy-Bertrand, Vincent Poindron, Francis Guillemin, Virginie Dufrost, Gary L. Norman, Thomas Lecompte, Jessie Risse, Bas de Laat, Denis Wahl, Hélène Desmurs-Clavel, Stéphane Zuily, RS: Carim - B01 Blood proteins & engineering, Biochemie, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Synapse Research Institute, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne et Immunologie Clinique (DMIIC - STRASBOURG), CHU Strasbourg, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Centre régional de compétence des Maladies systémiques et auto-immunes rares de l'adulte et Maladies vasculaires rares, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), INOVA Diagnostics, San Diego, and Université de Genève (UNIGE)
- Subjects
medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,1ST EPISODE ,030204 cardiovascular system & hematology ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Humans ,CLASSIFICATION CRITERIA ,Prospective Studies ,Activated Protein C Resistance ,LUPUS ANTICOAGULANTS ,030203 arthritis & rheumatology ,RISK ,Lupus anticoagulant ,REVISED CRITERIA ,biology ,business.industry ,RECOGNIZE ,Thrombosis ,General Medicine ,ASSOCIATION ,STANDARDIZATION ,medicine.disease ,Antiphospholipid Syndrome ,Cross-Sectional Studies ,beta 2-Glycoprotein I ,biology.protein ,Female ,AUTOANTIBODIES ,Activated protein C resistance ,Antibody ,business ,Protein C ,β2 glycoprotein i ,Cohort study ,medicine.drug ,GENERATION - Abstract
Background Antibodies binding to domain I of β2-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 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 β2-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.
- Published
- 2020