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

Alida L.P. Caforio*, Annalisa Angelini, Miri Blank, Alice Shani, Shaye Kivity, Gisele Goddard, Andrea Doria, Alessandro Schiavo, Martina Testolina, Stefania Bottaro, Renzo Marcolongo, Gaetano Thiene, Sabino Iliceto, Yehuda Shoenfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)166-177
Number of pages12
JournalInternational Journal of Cardiology
Volume179
DOIs
StatePublished - 20 Jan 2015

Keywords

  • Antibody
  • Immune system
  • Immunology
  • Myocarditis
  • Myosin

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