Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

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.

Mechanisms of action of antiphospholipid antibodies in the antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APS) is characterized by autoantibodies against negatively charged phospholipids in the serum, and clinically by multiple thromboses, thrombocytopenia, and recurrent fetal loss. The mechanism(s) by which the antibodies cause the clinical picture are not clear. We review the possible mechanisms of action of antiphospholipid (aPL) antibodies. Apparently, aPL antibodies act by interfering with coagulation, involving both endothelial cells, platelets, and humoral components, and affect pregnancy outcome by interfering with embryo implantation and fetal development.

Experimental models for antiphospholipid studies.

Three types of Experimental Animal Models have been used to investigate APA. 1) Passive transfer of APA to nocive mice. Branch et al injected pregnant Balb/c mice with purified IgG APA from patients with recurrent fetal loss. 2) Active immunization with APA. Backimer et al immunized Balb/c mice with a human monoclonal APA carrying the pathogenic idiotypes. 3) Immunization with beta 2 glycoprotein I (beta 2 GPI) (APA cofactor). Using affinity chromatography, we separated two distinct populations of antibodies. One was specific for beta 2GPI without binding to PL. Another population had a dual specificity for PL and beta 2GPI.

Ventricular arrhythmias in rehabilitated and nonrehabilitated post-myocardial infarction patients with left ventricular dysfunction.

The incidence of ventricular arrhythmias in rehabilitated post-myocardial infarction (MI) patients with left ventricular dysfunction included in a long-term rehabilitation program was assessed and compared with that in similar patients who were not in such a program. Thirty-eight post-MI patients (2 to 19 years after the acute event) with ejection fraction < 40% were investigated by 48-hour Holter monitoring. They were divided into the following 3 groups: group I, 11 patients who underwent arm training for 60 months; group II, 11 patients who underwent calisthenics for 36 months; and group III, 16 patients who were not in any rehabilitation program; the age of the patients was 61 +/- 7, 61 +/- 6 and 61 +/- 9 years, respectively, (p = not significant). Ejection fraction at rest was 31 +/- 9 for group I, 29 +/- 7 for group II, and 29 +/- 7 for group III (p = not significant). There were no significant differences concerning the location of MI, and antiarrhythmic treatment received by patients from all groups. At the conclusion of 48-hour Holter monitoring, 2 blood samples were obtained for assessment of norepinephrine (at rest and after postural change). Quality of life was determined by a detailed questionnaire, including questions concerning social activity, life satisfaction and sexual function. After 36 and 60 months, an improvement in hemodynamic condition of patients in group I was noted. Quality of life was higher in the rehabilitated patients, with enhanced emotional stability, satisfaction with work and social life, and a high percentage of return to work (82 vs 40%).(ABSTRACT TRUNCATED AT 250 WORDS)