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

Dongmei Yin, Walid Chayoua, Hilde Kelchtermans, Philip G. de Groot, Gary W. Moore, Jean-Christophe Gris, Stephane Zuily, Jacek Musial, Bas de Laat, Katrien M. J. Devreese*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)463-478
Number of pages16
JournalJournal of Thrombosis and Haemostasis
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • antiphospholipid syndrome
  • beta 2-glycoprotein I
  • domain I
  • multicenter
  • pregnancy morbidity
  • thrombosis
  • BETA(2)-GLYCOPROTEIN I
  • IGG ANTIBODIES
  • AUTOIMMUNE-DISEASES
  • BETA-2-GLYCOPROTEIN-I
  • THROMBOSIS
  • DIAGNOSIS
  • AUTOANTIBODIES
  • PATHOGENICITY
  • IMMUNOASSAY
  • ASSOCIATION

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