Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human β2-glycoprotein I

Jacob George, Miri Blank, Boris Gilburd, Maya Hojnik, Boris Shenkman, Iiia Tamarin, David Varon, Eiji Matsuura, Takao Koike, Yehuda Shoenfeld

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14 Citations (Scopus)

Abstract

β2-Glycoprotein I (β2GPI) is a 50 kDa molecule proposed as a principal target of 'autoimmune' antiphospholipid antibodies (aPL). We have used deleted mutants (DM) representing different domains of β2GPI (I-IV, IV-V and V) for immunization of naive mice and studied the characteristics of the respective murine IgG preparations in comparison with affinity-purified IgG from two patients with primary antiphospholipid syndrome. Immunization with β2GPI and with the DM produced anti-β2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with β2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of β2GPI (used for immunization) with resident negatively charged PL. Accordingly, DM which either lack the PL binding site or aPL attachment locus did not elicit, upon immunization, antibodies reactive with PL. Further, murine anti-β2GPI IgG and human 'autoimmune' aPL were similar, albeit not identical, in terms of DM requirement for PL binding and charge dependency. Murine antibodies and human aPL, regardless of their binding characteristics, were found to bind significantly to platelets upon their activation with thrombin and to promote platelet activation. The results of the current study emphasize the dissimilarities between human 'autoimmune' aPL and murine anti-β2GPI. Thus, anti-β2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided β2GPI is present.

Original languageEnglish
Pages (from-to)913-921
Number of pages9
JournalInternational Immunology
Volume9
Issue number6
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Antibodies
  • Antiphospholipid syndrome
  • Autoimmunity
  • Platelets
  • β-glycoprotein I

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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