Annexin A5 polymorphism (-1C-->T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome

Ann Rheum Dis. 2006 Nov;65(11):1468-72. doi: 10.1136/ard.2005.045237. Epub 2006 Jan 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / genetics
  • Abortion, Spontaneous / immunology
  • Adult
  • Annexin A5 / blood
  • Annexin A5 / genetics*
  • Annexin A5 / immunology
  • Antiphospholipid Syndrome / blood
  • Antiphospholipid Syndrome / genetics*
  • Antiphospholipid Syndrome / immunology
  • Autoantibodies / blood*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Polymorphism, Genetic*
  • Pregnancy
  • Risk Factors
  • Thrombosis / genetics
  • Thrombosis / immunology

Substances

  • Annexin A5
  • Autoantibodies
  • Immunoglobulin G
  • Immunoglobulin M