{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:10:07Z","timestamp":1791641407230,"version":"4.3.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"30","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Waugh Family Innovation"},{"name":"Labatt Family Heart Centre","award":["2019\u20132021"],"award-info":[{"award-number":["2019\u20132021"]}]},{"name":"Freeman Innovation Award"},{"name":"Heart and Stroke Richard Lewar Centre of Excellence"},{"name":"Caitlyn Elizabeth Morris Memorial Foundation"},{"name":"Alex Corrance Memorial Foundation"},{"name":"Carter Heart Rhythm Fellowship"},{"name":"Georg und Bertha Schwyzer-Winiker Foundation"},{"DOI":"10.13039\/501100007252","name":"Baugarten Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007252","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004362","name":"Swiss Heart Foundation","doi-asserted-by":"publisher","award":["GGP10186"],"award-info":[{"award-number":["GGP10186"]}],"id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in &amp;lt;25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3\/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be \u03b1-cardiac actin, \u03b1-skeletal actin, keratin, and connexin-43, vs. 0\/8 control subjects. All (18\/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0\/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A biomarker profile of autoantibodies against four cardiac proteins, namely \u03b1-cardiac actin, \u03b1-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaa383","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T11:09:11Z","timestamp":1587726551000},"page":"2878-2890","source":"Crossref","is-referenced-by-count":61,"title":["An autoantibody profile detects Brugada syndrome and identifies abnormally expressed myocardial proteins"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-8333","authenticated-orcid":false,"given":"Diptendu","family":"Chatterjee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Labatt Family Heart Centre and Translational Medicine, The Hospital for Sick Children & Research Institute and the University of Toronto , Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-4292","authenticated-orcid":false,"given":"Maurizio","family":"Pieroni","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, San Donato Hospital , Via Curtatone 54 - 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8093-1371","authenticated-orcid":false,"given":"Meena","family":"Fatah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Labatt Family Heart Centre and Translational Medicine, The Hospital for Sick Children & Research Institute and the University of Toronto , Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-0998","authenticated-orcid":false,"given":"Flavien","family":"Charpentier","sequence":"additional","affiliation":[{"name":"L\u2019Institut du Thorax, INSERM , CNRS, UNIV Nantes, 8 quai Moncousu, 44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher S","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , 27 King's College Circle, Toronto, Ontario M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2513-1627","authenticated-orcid":false,"given":"Danna A","family":"Spears","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Health Network\u2014Toronto General Hospital , 200 Elizabeth Street 4NU-492, Toronto, Ontario M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipashree","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Toronto , 27 King's College Circle, Toronto, Ontario M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4024-2974","authenticated-orcid":false,"given":"Gonca","family":"Suna","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Zurich , R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Martjin","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Windland Smith Rice Genetic Heart Rhythm Clinic , Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology , Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory , Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-8942","authenticated-orcid":false,"given":"Michael J","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Windland Smith Rice Genetic Heart Rhythm Clinic , Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology , Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory , Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-2501","authenticated-orcid":false,"given":"Eric","family":"Schulze-Bahr","sequence":"additional","affiliation":[{"name":"Institute for Genetics of Heart Diseases, Department f\u00fcr Kardiologie und Angiologie , Zentrum f\u00fcr Innere Medizin, Universit\u00e4tsklinikum M\u00fcnster Albert-Schweitzer-Campus 1, Geb\u00e4ude D3 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-711X","authenticated-orcid":false,"given":"Sven","family":"Dittmann","sequence":"additional","affiliation":[{"name":"Institute for Genetics of Heart Diseases, Department f\u00fcr Kardiologie und Angiologie , Zentrum f\u00fcr Innere Medizin, Universit\u00e4tsklinikum M\u00fcnster Albert-Schweitzer-Campus 1, Geb\u00e4ude D3 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0740-0464","authenticated-orcid":false,"given":"Pasquale G","family":"Notarstefano","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, San Donato Hospital , Via Curtatone 54 - 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-7870","authenticated-orcid":false,"given":"Leonardo","family":"Bolognese","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, San Donato Hospital , Via Curtatone 54 - 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4748-0158","authenticated-orcid":false,"given":"Firat","family":"Duru","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Zurich , R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-0803","authenticated-orcid":false,"given":"Ardan M","family":"Saguner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Zurich , R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-1278","authenticated-orcid":false,"given":"Robert M","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Labatt Family Heart Centre and Translational Medicine, The Hospital for Sick Children & Research Institute and the University of Toronto , Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"2022102512214106300_ehaa383-B1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/0735-1097(92)90253-J","article-title":"Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. 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