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Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

  • Meeting abstract
  • Open Access

Oxidation of beta2-glycoprotein I (beta2GPI) by the hydroxyl radical alters phospholipid binding and modulates recognition by anti-beta2GPI autoantibodies

  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Arthritis Research & Therapy20013(Suppl 2):P082

https://doi.org/10.1186/ar251

Received: 15 January 2001

Published: 26 January 2001

Keywords

  • Thiourea
  • Oxidative Modification
  • Antigenic Property
  • High Avidity
  • Dityrosine

We investigated whether β2GPI, the key antigen in the antiphospholipid syndrome, is susceptible to oxidative modifications by the hydroxyl radical (°OH) that may influence its lipid-binding and antigenic properties. We compared the effects on human and bovine β2GPI of °OH free radicals generated by γ -radiolysis of water with 137Cs and by the Fenton system composed of Fe-EDTA, ascorbate and H2O2. Radiolytic °OH caused a dose-dependent loss of tryptophan, production of dityrosine and carbonyl groups, dimerization and/or extensive aggregation of β2GPI. It ensued a reduction in affinity binding to cardiolipin liposomes and loss of β2GPI-dependent autoantibody binding to immobilized cardiolipin. Patient anti-β2GPI antibodies segregated into two groups based on the effect in the β2GPI-ELISA of β2GPI pretreatment with radiolytic °OH : enhancement or suppression of IgG binding in groups A (common type) and B (rare subset), respectively. The avidities of group A antibodies for fluid-phase β2GPI were low but increased in a dose-dependent manner upon β2GPI irradiation, in relation to protein crosslinking. Distinguishing features of group B antibodies included higher avidities for fluid-phase β2GPI that was no longer recognized after °OH treatment, and negative anticardiolipin tests suggesting epitope location near the phospholipid binding site. The °OH scavengers thiourea and mannitol efficiently protected against all above changes. In contrast, the Fenton system induced no major alteration in the structure and functions of β2GPI.

Thus, oxidative modifications of β2GPI via °OH attack of susceptible amino acids alters phospholipid binding, and modulates recognition by autoantibodies depending on their epitope specificities. These findings may be of clinical relevance for the generation and/or reactivity of anti-β2GPI antibodies.

Authors’ Affiliations

(1)
Laboratoire d'Immunologie, Institut de Synergie des Sciences et de la Santé, CHU Brest, France

Copyright

© BioMed Central Ltd 2001

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