title: Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice.
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.
authors.affiliation: Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. Electronic address: alida.caforio@unipd.it.
authors.forename: Alida L P
authors.initials: AL
authors.lastname: Caforio
authors.affiliation: Cardiovascular Pathology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Blank
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Alice
authors.initials: A
authors.lastname: Shani
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Shaye
authors.initials: S
authors.lastname: Kivity
authors.affiliation: Wolfson Medical Center, Holon, Sackler Faculty of Medicine Tel Aviv University, Israel.
authors.forename: Gisele
authors.initials: G
authors.lastname: Goddard
authors.affiliation: Division of Rheumatology, Dept of Experimental and Clinical Sciences University of Padua, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
authors.affiliation: Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Schiavo
authors.affiliation: Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Testolina
authors.affiliation: Clinical Pharmacology, Dept of Experimental and Clinical Sciences University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bottaro
authors.affiliation: Clinical Immunology, Dept of Medicine University of Padua, Padua, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Marcolongo
authors.affiliation: Cardiovascular Pathology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.affiliation: Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Iliceto
authors.affiliation: Schwartz-Kip Chair of Autoimmunity, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009205:Myocarditis / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D011446:Prospective Studies; D013045:Species Specificity; D055815:Young Adult
chemical_list: D001323:Autoantibodies
keywords: Antibody; Immune system; Immunology; Myocarditis; Myosin