title: Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.
abstract: Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) 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 beta 2GPI 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 beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the 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 beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-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 beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.
authors.affiliation: Department of Medicine, LSU Medical Centre, New Orleans 70112, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Aron
authors.forename: M L
authors.initials: ML
authors.lastname: Cuellar
authors.forename: R L
authors.initials: RL
authors.lastname: Brey
authors.forename: S
authors.initials: S
authors.lastname: Mckeown
authors.forename: L R
authors.initials: LR
authors.lastname: Espinoza
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: A E
authors.initials: AE
authors.lastname: Gharavi
mesh_terms: D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000032:analysis / Q000378:metabolism; D000974:Antibodies, Antinuclear / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology*; D001522:Behavior, Animal / Q000502:physiology; D004247:DNA / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D007117:Immunization, Secondary; D008098:Litter Size / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D010976:Platelet Count; D011247:Pregnancy; D012098:Reproduction / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; D004247:DNA