Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation
Abstract 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 panmy...
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| Format: | Article |
| Language: | English |
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Wiley
2020-06-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.12723 |
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| author | Andrea Frustaci Maurizio Scarpa Rosalia Maria da Riol Chiara Agrati Nicoletta Finato Romina Verardo Claudia Grande Cristina Chimenti Concetta Di Nora Matteo Antonio Russo Ugolini Livi |
| author_facet | Andrea Frustaci Maurizio Scarpa Rosalia Maria da Riol Chiara Agrati Nicoletta Finato Romina Verardo Claudia Grande Cristina Chimenti Concetta Di Nora Matteo Antonio Russo Ugolini Livi |
| author_sort | Andrea Frustaci |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-b3f2cf18504a455eab30ca7e14a1391d |
| institution | Kabale University |
| issn | 2055-5822 |
| language | English |
| publishDate | 2020-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-b3f2cf18504a455eab30ca7e14a1391d2025-02-03T10:25:46ZengWileyESC Heart Failure2055-58222020-06-01731331133710.1002/ehf2.12723Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantationAndrea Frustaci0Maurizio Scarpa1Rosalia Maria da Riol2Chiara Agrati3Nicoletta Finato4Romina Verardo5Claudia Grande6Cristina Chimenti7Concetta Di Nora8Matteo Antonio Russo9Ugolini Livi10Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences La Sapienza University Rome ItalyRegional Coordinating Center for Rare Diseases Udine University Hospital Rome ItalyRegional Coordinating Center for Rare Diseases Udine University Hospital Rome ItalyCellular Immunology Laboratory INMI L Spallanzani Rome ItalyDepartment of Medicine, Pathologic Anatomy Unit University of Udine Rome ItalyCellular and Molecular Cardiology Lab IRCCS L. Spallanzani Rome ItalyCellular and Molecular Cardiology Lab IRCCS L. Spallanzani Rome ItalyDepartment of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences La Sapienza University Rome ItalyCardiothoracic Surgery Udine University Hospital Rome ItalyMEBIC Consortium San Raffaele Open University Rome ItalyCardiothoracic Surgery Udine University Hospital Rome ItalyAbstract 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.https://doi.org/10.1002/ehf2.12723Fabry Diseasecardiomiopathyinflammation |
| spellingShingle | Andrea Frustaci Maurizio Scarpa Rosalia Maria da Riol Chiara Agrati Nicoletta Finato Romina Verardo Claudia Grande Cristina Chimenti Concetta Di Nora Matteo Antonio Russo Ugolini Livi Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation ESC Heart Failure Fabry Disease cardiomiopathy inflammation |
| title | Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation |
| title_full | Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation |
| title_fullStr | Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation |
| title_full_unstemmed | Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation |
| title_short | Fabry cardiomyopathy: Gb3‐induced auto‐reactive panmyocarditis requiring heart transplantation |
| title_sort | fabry cardiomyopathy gb3 induced auto reactive panmyocarditis requiring heart transplantation |
| topic | Fabry Disease cardiomiopathy inflammation |
| url | https://doi.org/10.1002/ehf2.12723 |
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