Fabry cardiomyopathy: Gb3-induced auto-reactive panmyocarditis requiring heart transplantation.

Autor: Frustaci A; Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, Rome, Italy., Scarpa M; Regional Coordinating Center for Rare Diseases, Udine University Hospital, Rome, Italy., Maria da Riol R; Regional Coordinating Center for Rare Diseases, Udine University Hospital, Rome, Italy., Agrati C; Cellular Immunology Laboratory, INMI L Spallanzani, Rome, Italy., Finato N; Department of Medicine, Pathologic Anatomy Unit, University of Udine, Rome, Italy., Verardo R; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy., Grande C; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy., Chimenti C; Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, Rome, Italy., Di Nora C; Cardiothoracic Surgery, Udine University Hospital, Rome, Italy., Russo MA; MEBIC Consortium, San Raffaele Open University, Rome, Italy.; Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana, Rome, Italy., Livi U; Cardiothoracic Surgery, Udine University Hospital, Rome, Italy.
Jazyk: angličtina
Zdroj: ESC heart failure [ESC Heart Fail] 2020 Jun; Vol. 7 (3), pp. 1331-1337. Date of Electronic Publication: 2020 Apr 29.
DOI: 10.1002/ehf2.12723
Abstrakt: Resistance to enzyme replacement therapy (ERT) is a major therapeutic challenge in Fabry disease (FD). Recent reports attribute to immune-mediated inflammation a main role in promoting disease progression and resistance to ERT. Aim of the study is to report a Gb3-induced auto-reactive panmyocarditis causing inefficacy of ERT and severe electrical instability, which required cardiac transplantation. Examining the explanted heart from a 57-year-old man with FD cardiomyopathy (CM) on 3-year ERT presenting incoming ventricular fibrillation, we documented a severe virus-negative myocarditis extended to cardiomyocytes, intramural coronary vessels, conduction tissue, and subepicardial ganglia. Serology was positive for anti-Gb3, anti-heart, and anti-myosin antibodies. In vitro Gb3 stimulation of patient's peripheral blood mononuclear cells (PBMC) induced high amount production of inflammatory cytokine IL1-β, IL-6, IL-8, and TNF-α. PBMC were stained using the monoclonal antibodies CD3-V500, CD4-V450, CD8-APCcy7, CD45RO-PerCPcy5.5 and CD27-FITC from BD Biosciences and CD56-PC7 from Bekman Coulter. The phenotypic analysis of PBMC showed a lower frequency of CD8 (9.2%) vs. 19.3% and NKT cells (1.6% vs. 2.4%) in Fabry patient respect to healthy donor, suggesting a possible homing to peripheral tissues. A Gb3-induced auto-reactive myocarditis is suggested as a possible cause of FDCM progression and ERT resistance. Immune-mediated inflammation of systemic Fabry cells may coexist and be controlled by implemental immunosuppressive therapy.
(© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)
Databáze: MEDLINE
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