Early onset of autoimmunity in MRL/++ mice following immunization with β2 glycoprotein I

A. L. Aron, M. L. Cuellar, R. L. Brey, S. McKeown, L. R. Espinoza, Y. Shoenfeld, A. E. Gharavi

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Abstract

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with β2 glycoprotein I (β2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by β2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with β2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all β2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting crossreactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in β2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that β2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.

Original languageEnglish (US)
Pages (from-to)78-81
Number of pages4
JournalClinical and Experimental Immunology
Volume101
Issue number1
StatePublished - Jan 1 1995

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Keywords

  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Fetal death
  • Thrombocytopenia
  • β glycoprotein I

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Aron, A. L., Cuellar, M. L., Brey, R. L., McKeown, S., Espinoza, L. R., Shoenfeld, Y., & Gharavi, A. E. (1995). Early onset of autoimmunity in MRL/++ mice following immunization with β2 glycoprotein I. Clinical and Experimental Immunology, 101(1), 78-81.