{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:35:16Z","timestamp":1790714116730,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["LE 3570\/2-1; 3570\/3-1"],"award-info":[{"award-number":["LE 3570\/2-1; 3570\/3-1"]}]},{"name":"Bundesministerium f\u00fcr Forschung","award":["01KC2006B"],"award-info":[{"award-number":["01KC2006B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment. Nevertheless, their increasing use leads to an increase of immune-related adverse events (irAEs). Among them, ICI-associated myocarditis (ICIM) is a rare irAE with a high mortality rate. We aimed to characterize the transcriptional changes of ICIM myocardial biopsies and their possible implications. Patients suspected for ICIM were assessed in the cardio-oncology units of University Hospitals Heidelberg and Kiel. Via RNA sequencing of myocardial biopsies, we compared transcriptional changes of ICIM (n = 9) with samples from dilated cardiomyopathy (DCM, n = 11), virus-induced myocarditis (VIM, n = 5), and with samples of patients receiving ICIs without any evidence of myocarditis (n = 4). Patients with ICIM (n = 19) showed an inconsistent clinical presentation, e.g., asymptomatic elevation of cardiac biomarkers (hs-cTnT, NT-proBNP, CK), a drop in left ventricular ejection fraction, or late gadolinium enhancement in cMRI. We found 3784 upregulated genes in ICIM (FDR &lt; 0.05). In the overrepresented pathway \u2018response to interferon-gamma\u2019, we found guanylate binding protein 5 and 6 (compared with VIM: GBP5 (log2 fc 3.21), GBP6 (log2 fc 5.37)) to be significantly increased in ICIM on RNA- and protein-level. We conclude that interferon-gamma and inflammasome-regulating proteins, such as GBP5, may be of unrecognized significance in the pathophysiology of ICIM.<\/jats:p>","DOI":"10.3390\/cancers13102498","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T11:45:57Z","timestamp":1621511157000},"page":"2498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Comparative Transcriptomics of Immune Checkpoint Inhibitor Myocarditis Identifies Guanylate Binding Protein 5 and 6 Dysregulation"],"prefix":"10.3390","volume":"13","author":[{"given":"Daniel","family":"Finke","sequence":"first","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Cardio-Oncology Unit, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3085-1282","authenticated-orcid":false,"given":"Markus","family":"Heckmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Cardio-Oncology Unit, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janek","family":"Salatzki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Riffel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Herpel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Heinzerling","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Meder","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"V\u00f6lkers","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8223-2638","authenticated-orcid":false,"given":"Oliver","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Kiel, 24105 Kiel, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 24105 Partner Site Kiel\/Hamburg\/L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Katus","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Leuschner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-0836","authenticated-orcid":false,"given":"Ziya","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-8580","authenticated-orcid":false,"given":"Lorenz","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Cardio-Oncology Unit, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 69120 Partner Site Heidelberg\/Mannheim, Germany"},{"name":"Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","article-title":"Immune checkpoint inhibitors: Recent progress and potential biomarkers","volume":"50","author":"Darvin","year":"2018","journal-title":"Exp. 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