Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice

Int J Cardiol. 2015 Jan 20:179:166-77. doi: 10.1016/j.ijcard.2014.10.165. Epub 2014 Oct 29.

Abstract

Background: Human autoimmune myocarditis is characterized by an increased frequency of serum organ and disease-specific anti-heart autoantibodies (AHA) in affected patients. To assess whether AHA are directly pathogenic, we used the passive transfer technique of AHA from patients to normal Balb/c mice to induce an experimental myocarditis.

Methods: In keeping with a classical passive transfer experiment, sera from 5 AHA positive myocarditis patients (3 male, mean age 30 ± 11 years, 3 with giant cell and 2 with lymphocytic myocarditis) were affinity purified and injected into 25 Balb/c mice. As controls, affinity purified sera from 5 healthy donors were passively transferred to 25 Balb/c mice. Further 15 control mice were injected with phosphate-buffered saline and 9 mice did not receive any injection. In all patients cardiac-specific AHA of IgG class had been previously detected by an indirect immunofluorescence (IFL) technique on cryostat sections of O blood group human heart. The animals were sacrificed after 4 weeks and the hearts were blindly examined for histological evidence of myocarditis by an expert cardiac pathologist.

Results: Myocarditis was present in 13/25 (52%) of the mice which received affinity-purified IgG from patients. The findings of severe, moderate or mild myocarditis were more common in the mice which received affinity-purified IgG from patients (20%; 20% and 12%) than in control animals (2%, p=0.01; 0%, p=0.003; and 0%, p=0.04 respectively).

Conclusions: These findings provide a new evidence for AHA-mediated pathogenicity in human myocarditis, according to Rose-Witebsky criteria.

Keywords: Antibody; Immune system; Immunology; Myocarditis; Myosin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Female
  • Humans
  • Immunization, Passive / methods*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Myocarditis / blood*
  • Myocarditis / immunology
  • Myocarditis / pathology*
  • Myocardium / immunology
  • Myocardium / pathology*
  • Prospective Studies
  • Species Specificity
  • Young Adult

Substances

  • Autoantibodies