The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study

J Thromb Haemost. 2009 Nov;7(11):1767-73. doi: 10.1111/j.1538-7836.2009.03588.x. Epub 2009 Aug 19.


Background: Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti-beta2-glycoprotein I (beta 2GPI) antibodies play a central role in the disease process of APS.

Objectives: We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta 2GPI and thrombosis/pregnancy morbidity in an international multicenter study.

Patients/methods: Four hundred and seventy-seven patients derived from nine different centres met the inclusion criterion of having anti-beta 2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2GPI antibodies were established at the different centres of inclusion. After being re-tested for the presence of IgG and/or IgM anti-beta 2GPI antibodies, the samples were tested for the presence of IgG-directed against domain I of beta 2GPI and results were correlated with the thrombotic and obstetric history.

Results: Re-testing for the presence of anti-beta 2GPI antibodies resulted in inclusion of 442/477 patients. IgG class anti-domain I antibodies were present in plasma of 243/442 patients (55%). 201/243 (83%) had a history of thrombosis. This resulted in an odds ratio of 3.5 (2.3-5.4, 95% confidence interval) for thrombosis. Anti-domain I IgG antibodies were also significantly correlated with obstetric complications [odds ratio: 2.4 (1.4-4.3, 95% confidence interval)].

Conclusion: In this multicenter study, the detection of IgG antibodies that are directed against domain I of beta 2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti-beta 2GPI antibody assay.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Antiphospholipid
  • Antiphospholipid Syndrome / diagnosis
  • Antiphospholipid Syndrome / immunology
  • Autoantibodies / blood*
  • Epitopes / immunology*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications / immunology
  • Thrombosis / diagnosis
  • Thrombosis / immunology*
  • Young Adult
  • beta 2-Glycoprotein I / immunology*


  • Antibodies, Antiphospholipid
  • Autoantibodies
  • Epitopes
  • Immunoglobulin G
  • beta 2-Glycoprotein I