Dongmei Yin1,2, Walid Chayoua1,2, Hilde Kelchtermans1,2, Philip G de Groot2, Gary W Moore3, Jean-Christophe Gris4,5, Stéphane Zuily6, Jacek Musial7, Bas de Laat1,2, Katrien M J Devreese8. 1. Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands. 2. Synapse Research Institute, Maastricht, the Netherlands. 3. Viapath Analytics, Department of Haemostasis and Thrombosis, Guy's and St Thomas' Hospitals, London, UK. 4. Department of Haematology, University Hospital of Nîmes and University of Montpellier, Montpellier, France. 5. Ivan Sechenov First Moscow State Medical University, Moscow, Russia. 6. Inserm, DCAC, Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, Centre Hospitalier Regional Universitaire de Nancy, Université de Lorraine, Nancy, France. 7. Department of Internal Medicine, Allergy and Immunology, Jagiellonian University Medical College, Kraków, Poland. 8. Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
Abstract
BACKGROUND: Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-β2glycoprotein I (β2GPI) proved to be pathogenic, but are not included in the current classification criteria. OBJECTIVES: Investigate the clinical value of detecting anti-DI IgG in APS. PATIENTS/ METHODS: From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-β2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash® β2GPI domain I assay. RESULTS: Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-β2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-β2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. CONCLUSIONS: Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-β2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash® did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.
BACKGROUND: Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-β2glycoprotein I (β2GPI) proved to be pathogenic, but are not included in the current classification criteria. OBJECTIVES: Investigate the clinical value of detecting anti-DI IgG in APS. PATIENTS/ METHODS: From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-β2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash® β2GPI domain I assay. RESULTS: Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-β2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-β2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. CONCLUSIONS: Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-β2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash® did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.
Authors: Pavla Bradacova; Ludek Slavik; Jana Ulehlova; Adela Skoumalova; Jana Ullrychova; Jana Prochazkova; Antonin Hlusi; Gayane Manukyan; Eva Kriegova Journal: Biomedicines Date: 2021-02-08