Detection of anti-domain I antibodies by chemiluminescence enables the identification of high-risk antiphospholipid syndrome patients: A multicenter multiplatform study.

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.

• Authors: Dongmei Yin, Walid Chayoua, Hilde Kelchtermans, Philip G de Groot, Gary W Moore, Jean-Christophe Gris, Stéphane Zuily, Jacek Musial, Bas de Laat, Katrien M J Devreese
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 18 Issue 2 Pg. 463-478 (02 2020) ISSN: 1538-7836 [Electronic] England
• PMID: 31749277 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2019 International Society on Thrombosis and Haemostasis.

Chemical References

• Antibodies, Anticardiolipin
• Epitopes
• Immunoglobulin G
• Lupus Coagulation Inhibitor
• beta 2-Glycoprotein I

Topics

• Adult
• Aged
• Antibodies, Anticardiolipin (blood, immunology)
• Antiphospholipid Syndrome (immunology)
• Epitopes (chemistry)
• Female
• Humans
• Immunoglobulin G (blood, immunology)
• Luminescence
• Lupus Coagulation Inhibitor (immunology)
• Male
• Middle Aged
• Odds Ratio
• Pregnancy
• Pregnancy Complications, Cardiovascular (immunology)
• Protein Domains
• Reproducibility of Results
• beta 2-Glycoprotein I (chemistry, immunology)