{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:42:23Z","timestamp":1769085743549,"version":"3.49.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":2060,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Telethon","doi-asserted-by":"publisher","award":["GGP17055"],"award-info":[{"award-number":["GGP17055"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP17055"],"award-info":[{"award-number":["GGP17055"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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-\u03b2, IL-6, IL-8, and TNF-\u03b1. 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.<\/jats:p>","DOI":"10.1002\/ehf2.12723","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T03:53:00Z","timestamp":1588132380000},"page":"1331-1337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Fabry Cardiomyopathy: Gb3-Induced Auto-Reactive Panmyocarditis Requiring Heart Transplantation"],"prefix":"10.1093","volume":"7","author":[{"given":"Andrea","family":"Frustaci","sequence":"first","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Regional Coordinating Center for Rare Diseases, Udine University Hospital , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalia","family":"Maria da Riol","sequence":"additional","affiliation":[{"name":"Regional Coordinating Center for Rare Diseases, Udine University Hospital , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Agrati","sequence":"additional","affiliation":[{"name":"Cellular Immunology Laboratory, INMI L Spallanzani , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Finato","sequence":"additional","affiliation":[{"name":"Department of Medicine, Pathologic Anatomy Unit, University of Udine , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Verardo","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Grande","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Di Nora","sequence":"additional","affiliation":[{"name":"Cardiothoracic Surgery, Udine University Hospital , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo Antonio","family":"Russo","sequence":"additional","affiliation":[{"name":"MEBIC Consortium, San Raffaele Open University , Rome ,","place":["Italy"]},{"name":"Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana , Rome 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