Alida L P Caforio1, Annalisa Angelini2, Miri Blank3, Alice Shani3, Shaye Kivity3, Gisele Goddard4, Andrea Doria5, Alessandro Schiavo6, Martina Testolina6, Stefania Bottaro7, Renzo Marcolongo8, Gaetano Thiene2, Sabino Iliceto6, Yehuda Shoenfeld9. 1. Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. Electronic address: alida.caforio@unipd.it. 2. Cardiovascular Pathology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. 3. The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel. 4. Wolfson Medical Center, Holon, Sackler Faculty of Medicine Tel Aviv University, Israel. 5. Division of Rheumatology, Dept of Experimental and Clinical Sciences University of Padua, Padua, Italy. 6. Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. 7. Clinical Pharmacology, Dept of Experimental and Clinical Sciences University of Padua, Padua, Italy. 8. Clinical Immunology, Dept of Medicine University of Padua, Padua, Italy. 9. Schwartz-Kip Chair of Autoimmunity, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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.
BACKGROUND:Humanautoimmune 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 myocarditispatients (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 humanmyocarditis, according to Rose-Witebsky criteria.
Authors: Heinz-Peter Schultheiss; DeLisa Fairweather; Alida L P Caforio; Felicitas Escher; Ray E Hershberger; Steven E Lipshultz; Peter P Liu; Akira Matsumori; Andrea Mazzanti; John McMurray; Silvia G Priori Journal: Nat Rev Dis Primers Date: 2019-05-09 Impact factor: 65.038
Authors: Agata Tymińska; Krzysztof Ozierański; Aleksandra Skwarek; Agnieszka Kapłon-Cieślicka; Anna Baritussio; Marcin Grabowski; Renzo Marcolongo; Alida Lp Caforio Journal: J Pers Med Date: 2022-01-30
Authors: Carsten Tschöpe; Enrico Ammirati; Biykem Bozkurt; Alida L P Caforio; Leslie T Cooper; Stephan B Felix; Joshua M Hare; Bettina Heidecker; Stephane Heymans; Norbert Hübner; Sebastian Kelle; Karin Klingel; Henrike Maatz; Abdul S Parwani; Frank Spillmann; Randall C Starling; Hiroyuki Tsutsui; Petar Seferovic; Sophie Van Linthout Journal: Nat Rev Cardiol Date: 2020-10-12 Impact factor: 49.421