Volume 5 Supplement 1

23rd European Workshop for Rheumatology Research

Open Access

The infectious origin of the antiphospholipid syndrome: induction by passive transfer of anti-β2GPI antibodies induced by common bacteria

  • M Blank,
  • I Krause1,
  • M Fridkin2,
  • N Keller1,
  • J Kopolovic1,
  • I Goldberg1,
  • A Tobar1 and
  • Y Shoenfeld1
Arthritis Res Ther20035(Suppl 1):14

DOI: 10.1186/ar644

Received: 14 January 2003

Published: 24 February 2003

The antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against β2-glycoprotein I (β2GPI). The factors causing production of anti-β2GPI remain unidentified, but an association with infectious agents has been reported. We recently identified a hexapeptide (TLRVYK) that is recognized specifically by a pathogenic anti-β2GPI monoclonal antibody. In the present study we evaluated the APS-related pathogenic potential of microbial pathogens, which share structural homology with the this hexapeptide. Mice were immunized with a panel of TLRVYK-related microbial particles and were studied for the development of mouse anti-β2GPI autoantibodies. Mouse IgG specific to the TLRVYK peptide were affinity purified from the immunized mice and passively infused i.v. into naive mice at day 0 of pregnancy. APS parameters were evaluated in the infused mice on day 15 of pregnancy. Following immunization, high titers of anti-peptide, anti-β2GPI antibodies were observed in mice immunized with Haemophilus influenzae, Neisseria gonorrhoeae or tetanus toxoid. Naive mice infused with the affinity-purified anti-peptide antibodies had a significant thrombocytopenia, prolonged aPTT and elevated percentage of fetal loss, similar to the findings in a control group of mice immunized with a pathogenic anti-β2GPI monoclonal antibody. Our study establishes a mechanism of molecular mimicry in experimental APS, demonstrating that bacteria homologous with β2GPI structure are able to induce the generation of pathogenic anti-β2GPI antibodies along with APS manifestations.

Authors’ Affiliations

(1)
Center for of Autoimmune Diseases, Department of Internal Medicine 'B', The Weizmann Institute of Science
(2)
Department of Organic Chemistry, The Weizmann Institute of Science

Copyright

© The Author(s) 2003

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