1. Detection of anti‐domain I antibodies by chemiluminescence enables the identification of high‐risk antiphospholipid syndrome patients: A multicenter multiplatform study
- Author
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Dongmei Yin, Katrien Devreese, Walid Chayoua, Gary W. Moore, Bas de Laat, Jacek Musiał, Hilde Kelchtermans, Jean-Christophe Gris, Stéphane Zuily, Philip G. de Groot, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Synapse Research Institute, Guy's and St Thomas' Hospitals, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Sechenov First Moscow State Medical University, 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), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Ghent University Hospital, Biochemie, and RS: Carim - B01 Blood proteins & engineering
- Subjects
Male ,Luminescence ,MESH: Pregnancy Complications, Cardiovascular ,multicenter ,030204 cardiovascular system & hematology ,Gastroenterology ,Epitope ,Epitopes ,MESH: Pregnancy ,0302 clinical medicine ,Pregnancy ,Odds Ratio ,beta 2-glycoprotein I ,MESH: Aged ,MESH: Immunoglobulin G ,BETA(2)-GLYCOPROTEIN I ,Lupus anticoagulant ,MESH: Middle Aged ,Hematology ,MESH: Beta 2-Glycoprotein I ,medicine.diagnostic_test ,biology ,MESH: Luminescence ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,ASSOCIATION ,Middle Aged ,pregnancy morbidity ,3. Good health ,MESH: Reproducibility of Results ,Lupus Coagulation Inhibitor ,MESH: Protein Domains ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,BETA-2-GLYCOPROTEIN-I ,Female ,Antibody ,Adult ,medicine.medical_specialty ,MESH: Epitopes ,MESH: Lupus Coagulation Inhibitor ,Pregnancy Complications, Cardiovascular ,DIAGNOSIS ,AUTOIMMUNE-DISEASES ,IMMUNOASSAY ,03 medical and health sciences ,Protein Domains ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Antiphospholipid syndrome ,Internal medicine ,MESH: Antiphospholipid Syndrome ,medicine ,Humans ,Beta 2-Glycoprotein I ,Aged ,MESH: Humans ,β2-glycoprotein I ,business.industry ,MESH: Antibodies, Anticardiolipin ,IGG ANTIBODIES ,Autoantibody ,Reproducibility of Results ,MESH: Adult ,medicine.disease ,MESH: Male ,MESH: Odds Ratio ,THROMBOSIS ,domain I ,Antibodies, Anticardiolipin ,Immunoglobulin G ,Immunoassay ,biology.protein ,AUTOANTIBODIES ,business ,MESH: Female ,antiphospholipid syndrome ,PATHOGENICITY - Abstract
Background Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-beta 2glycoprotein I (beta 2GPI) 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-beta 2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash (R) beta 2GPI 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-beta 2GPI 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-beta 2GPI 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-beta 2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash (R) 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.
- Published
- 2020
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