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Annexin A5 polymorphism (−1C→T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome
  1. B de Laat1,
  2. R H W M Derksen2,
  3. I J Mackie3,
  4. M Roest4,
  5. S Schoormans5,
  6. B J Woodhams6,
  7. P G de Groot1,
  8. W L van Heerde5
  1. 1Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht
  3. 3Haemostasis Research Unit, Department of Haematology, University College London, London, UK
  4. 4Department of Clinical Chemistry, University Medical Center Utrecht
  5. 5Central Laboratory of Haematology of the Radboud University Nijmegen Medical Center Nijmegen, Nijmegen, The Netherlands
  6. 6Stago R&D, Gennevilliers, France
  1. Correspondence to:
    P G de Groot
    Thrombosis and Haemostasis Laboratory, Department of Haematology, G03.647, University Medical Center Utrecht, PO Box 85500, 3584CX Utrecht, The Netherlands;Ph.G.deGroot{at}


Background: Annexin A5 is thought to have a role in the pathophysiology of the antiphospholipid syndrome (APS)—a syndrome characterised by recurrent thrombosis and pregnancy morbidity.

Objective: To investigate whether anti-annexin A5 immunoglobulin (Ig)M or IgG antibodies, or the −1C→T polymorphism of annexin A5, is a risk factor for thrombosis or miscarriage, and whether the −1C→T polymorphism is correlated with APS.

Methods: A cohort study was carried out with a population of 198 patients with primary APS, systemic lupus erythematosus or lupus-like disease. For the detection of anti-annexin A5 antibodies and the measurement of annexin A5 plasma levels, ELISA-type methods were used. The annexin A5 −1C→T mutation was detected by restriction fragment length polymorphism.

Results: 71 patients were positive for annexin A5 IgM or IgG antibodies, of whom 53 patients were positive for anti-annexin A5 IgG antibodies and 27 of 198 patients were positive for anti-annexin A5 IgM antibodies. The prevalence of IgM or IgG anti-annexin A5 antibodies was not significantly associated with thrombosis or miscarriage on multivariate analysis. The prevalence of the −1C→T mutation in the annexin A5 gene (46/198 patients) was significantly associated with miscarriage (odds ratio 2.7, 95% confidence interval 1.1 to 6.7, independent risk factor).

Conclusion: The detection of anti-annexin A5 antibodies does not seem relevant for estimating the risk for thrombosis or miscarriage in APS. The −1C→T mutation was an independent risk factor for miscarriage, which is independent of APS.

  • APS, antiphospholipid syndrome
  • β2-GPI, β2-glycoprotein I
  • IQR, interquartile range
  • LAC, lupus anticoagulant
  • LLD, lupus-like disease
  • PCR, polymerase chain reaction
  • PTT-LA, partial thromboplastin time-lupus anticoagulant
  • RVVT, Russell’s viper venom time
  • SLE, systemic lupus erythematosus
  • TBS, Tris-buffered saline

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  • Published Online First 31 January 2006

  • Competing interests: All authors except BJW certify that they have no affiliation with or financial involvement in any organisation, or entity with a direct financial interest in the subject matter or materials discussed in this manuscript (eg, employment, consultancies, stock ownership, honoraria), except as disclosed in an attachment or cover letter. BJW is an employee of Stago R&D. He provided the anti-annexin A5 kits and was of technical assistance in several experiments. Being employed by Stago R&D had no influence on BJW’s collection, presentation and interpretation of the data. Any research or project support is identified in the Acknowledgements.

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