The clinical value of assays detecting antibodies against domain I of beta 2-glycoprotein I in the antiphospholipid syndrome

Dongmei Yin, Bas de Laat, Katrien M. J. Devreese, Hilde Kelchtermans*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

20 Citations (Web of Science)

Abstract

As the clinical symptoms of the antiphospholipid syndrome (APS) frequently occur irrespective of the syndrome, diagnosis predominantly depends on the laboratory assays measuring the level or function of antiphospholipid antibodies (aPLs). beta 2-glycoprotein I (beta 2GPI) is increasingly accepted as the most important target of aPLs. Anti-beta 2GPI antibodies constitute a heterogeneous population, but current in vivo and in vitro evidence show that especially the first domain (DI) of beta 2GPI contains an important pathogenic epitope. This epitope containing Glycine40-Arginine43 (G40-R43) has proven to be cryptic and only exposed when beta 2GPI is in its open conformation. A previous study demonstrated a highly variable exposure of the cryptic epitope in commercial anti-beta 2GPI assays, with implications on correct patient classification. Unexpectedly, recent unpublished data revealed impaired exposure of the pathogenic epitope in the commercially available anti-DI chemiluminescence immunoassay (CIA) assay detecting specific antibodies directed to DI.

In this review we summarize the laboratory and clinical performance characteristics of the different anti-DI assays in published data and conclude with inconsistent results for both the correlation of anti-DI antibodies with clinical symptoms and the added value of anti-DI antibodies in the classification criteria of APS. Additionally, we hypothesize on possible explanations for the observed discrepancies. Finally, we highly advise manufacturers to use normal pooled plasma spiked with the monoclonal anti-DI antibodies to verify correct exposure of the cryptic epitope.

Original languageEnglish
Pages (from-to)1210-1218
Number of pages9
JournalAutoimmunity Reviews
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 2018

Keywords

  • Antiphospholipid syndrome
  • Antiphospholipid antibody
  • beta 2-glycoprotein I
  • Domain I
  • Assay
  • Thrombosis
  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • BETA(2)-GLYCOPROTEIN I
  • IGG ANTIBODIES
  • ANTI-BETA(2)-GLYCOPROTEIN-I ANTIBODIES
  • CHEMILUMINESCENCE IMMUNOASSAY
  • CLASSIFICATION CRITERIA
  • RISK STRATIFICATION
  • AUTOIMMUNE-DISEASES
  • EUROPEAN-FORUM
  • AUTOANTIBODIES

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