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

• Published in: Journal of thrombosis and haemostasis 2009-11, Vol.7 (11), p.1767-1773
• Main Authors: DE LAAT, B., PENGO, V., PABINGER, I., MUSIAL, J., VOSKUYL, A. E., BULTINK, I. E. M., RUFFATTI, A., ROZMAN, B., KVEDER, T., DE MOERLOOSE, P., BOEHLEN, F., RAND, J., ULCOVA‐GALLOVA, Z., MERTENS, K., DE GROOT, P. G.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; antiphospholipid syndrome; Antiphospholipid Syndrome - diagnosis; Antiphospholipid Syndrome - immunology; Autoantibodies - blood; beta 2-Glycoprotein I - immunology; beta2‐glycoprotein I; domain I; Epitopes - immunology; Female; Humans; Immunoglobulin G - blood; Male; Middle Aged; obstetric complication; Pregnancy; Pregnancy Complications - immunology; thrombosis; Thrombosis - diagnosis; Thrombosis - immunology; Young Adult
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2009.03588.x

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 (beta2GPI) 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 beta2GPI 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‐beta2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti‐cardiolipin antibodies and anti‐beta2GPI antibodies were established at the different centres of inclusion. After being re‐tested for the presence of IgG and/or IgM anti‐beta2GPI antibodies, the samples were tested for the presence of IgG‐directed against domain I of beta2GPI and results were correlated with the thrombotic and obstetric history. Results: Re‐testing for the presence of anti‐beta2GPI 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 beta2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti‐beta2GPI antibody assay.