Detection of anti‐domain I antibodies by chemiluminescence enables the identification of high‐risk antiphospholipid syndrome patients: A multicenter multiplatform study. (30th January 2020)

• Record Type: Journal Article
• Authors: Yin, Dongmei; Chayoua, Walid; Kelchtermans, Hilde; de Groot, Philip G.; Moore, Gary W.; Gris, Jean‐Christophe; Zuily, Stéphane; Musial, Jacek; de Laat, Bas; Devreese, Katrien M. J.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 18:Number 2(2020)
• Page Start: 463
• Page End: 478
• Publication Date: 2020-01-30
• Subjects: antiphospholipid syndrome -- β2‐glycoprotein I -- domain I -- multicenter -- pregnancy morbidity -- thrombosis; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.14682
• Languages: English
• ISSNs: 1538-7933

Abstract

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.