{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:22:29Z","timestamp":1787505749223,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Budget Integrato per la Ricerca dei Dipartimenti (BIRD, year 2019), Padova University, Padova, Italy","award":["RF-2019-12370183"],"award-info":[{"award-number":["RF-2019-12370183"]}]},{"name":"Italian Ministry of Health, Target Research, Rome, Italy, year 2019","award":["RF-2019-12370183"],"award-info":[{"award-number":["RF-2019-12370183"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Autoantibodies against Desmoglein-2 desmosomal protein (anti-DSG2-ab) were identified in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) by Enzyme-Linked ImmunoSorbent Assay (ELISA); anti-intercalated disk autoantibodies (AIDAs) were identified in myocarditis and (ARVC) by indirect immunofluorescence (IFL). We aim to assess: (1) anti-DSG2-ab specificity in ARVC and myocarditis, (2) accuracy of anti-DSG2-ab detection by ELISA versus AIDA by IFL, and (3) clinical correlates of anti-DSG2-ab in ARVC. Methods: We included 77 patients with ARVC, 91 with myocarditis\/dilated cardiomyopathy (DCM), 27 with systemic immune-mediated diseases, and 50 controls. Anti-heart antibodies (AHAs) and AIDAs were assessed by IFL, and anti-DSG2-ab by ELISA (assessed both by optical density, OD, and U\/L). Receiving operator curve (ROC) analysis was used to assess ELISA diagnostic accuracy. Results: A relevant proportion (56%) of ARVC patients was anti-DSG2-ab-positive, with higher anti-DSG2-ab levels than controls. Anti-DSG2-ab titer was not different between ARVC and myocarditis\/DCM patients (48% anti-DSG-ab positive). Frequency of anti-DSG2 positivity by ELISA was higher in AIDA-positive cases by IFL than AIDA-negative cases (p = 0.039 for OD, p = 0.023 for U\/L). In ARVC, AIDA-positive patients were more likely to be AHA-positive (p &lt; 0.001), had pre-syncope (p = 0.025), and abnormalities in cardiac rhythm (p = 0.03) than ARVC AIDA-negative patients, while anti-DSG2-ab positivity did not have clinical correlates. Conclusions: Anti-DG2-ab detection in ARVC and myocarditis\/DCM reflects immune-mediated pathogenesis to desmosomal proteins. Higher frequency of anti-DSG2-ab positivity by ELISA by U\/L was higher in AIDA-positive cases by IFL than AIDA-negative cases, in keeping with the hypothesis that DSG2 is one of AIDA autoantigens. In ARVC, AIDA status but not anti-DSG2-ab showed distinct clinical correlates, possibly reflecting a wider AIDA autoantigenic spectrum.<\/jats:p>","DOI":"10.3390\/jcm13226736","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T03:53:14Z","timestamp":1731383594000},"page":"6736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prevalence and Correlates of Anti-DSG2 Antibodies in Arrhythmogenic Right Ventricular Cardiomyopathy and Myocarditis: Immunological Insights from a Multicenter Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-077X","authenticated-orcid":false,"given":"Andrea Silvio","family":"Giordani","sequence":"first","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pontara","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Vicenzetto","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Baritussio","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Peloso Cattini","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bison","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Re","sequence":"additional","affiliation":[{"name":"Cardiology Division, San Camillo Hospital, 00152 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5306-1785","authenticated-orcid":false,"given":"Renzo","family":"Marcolongo","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaylyn","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Labatt Family Heart Centre and Translational Medicine, The Hospital for Sick Children & Research Institute, The University of Toronto, Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diptendu","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Labatt Family Heart Centre and Translational Medicine, The Hospital for Sick Children & Research Institute, The University of Toronto, Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, The University of Toronto, Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-1278","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, The University of Toronto, Room 1725D, 555 University Avenue, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-5655","authenticated-orcid":false,"given":"Alida Linda Patrizia","family":"Caforio","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1093\/eurheartj\/ehu493","article-title":"The research venture in arrhythmogenic right ventricular cardiomyopathy: A paradigm of translational medicine","volume":"36","author":"Thiene","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1161\/CIRCULATIONAHA.115.020254","article-title":"Sudden Cardiac Death in the Young","volume":"133","author":"Ackerman","year":"2016","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e301","DOI":"10.1016\/j.hrthm.2019.05.007","article-title":"2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy","volume":"16","author":"Towbin","year":"2019","journal-title":"Heart Rhythm"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijcard.2020.06.005","article-title":"Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria","volume":"319","author":"Corrado","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1086\/504393","article-title":"DSG2 Mutations Contribute to Arrhythmogenic Right Ventricular Dysplasia\/Cardiomyopathy","volume":"79","author":"Awad","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1086\/521633","article-title":"A Novel Dominant Mutation in Plakoglobin Causes Arrhythmogenic Right Ventricular Cardiomyopathy","volume":"81","author":"Asimaki","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1056\/NEJMoa0808138","article-title":"A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy","volume":"360","author":"Asimaki","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.yjmcc.2020.03.006","article-title":"A homozygous DSC2 deletion associated with arrhythmogenic cardiomyopathy is caused by uniparental isodisomy","volume":"141","author":"Brodehl","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.1016\/j.jmb.2013.07.035","article-title":"Mechanistic Basis of Desmosome-Targeted Diseases","volume":"425","author":"Bikker","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/08916930701619235","article-title":"Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy","volume":"41","author":"Caforio","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1093\/eurheartj\/ehy567","article-title":"An autoantibody identifies arrhythmogenic right ventricular cardiomyopathy and participates in its pathogenesis","volume":"39","author":"Chatterjee","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/oxfordjournals.eurheartj.a015230","article-title":"Circulating cardiac-specific autoantibodies as markers of autoimmunity in clinical and biopsy-proven myocarditis. The Myocarditis Treatment Trial Investigators","volume":"18","author":"Caforio","year":"1997","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1111\/bjd.19342","article-title":"Mutations in genes encoding desmosomal proteins: Spectrum of cutaneous and extracutaneous abnormalities","volume":"184","author":"Lee","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_14","first-page":"907","article-title":"\u201cHot phase\u201d clinical presentation in arrhythmogenic cardiomyopathy","volume":"23","author":"Bariani","year":"2021","journal-title":"EP Eur."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ehaa946.2103","DOI":"10.1093\/ehjci\/ehaa946.2103","article-title":"Myocarditis and arrhythmogenic right ventricular cardiomyopathy: A diagnostic challenge","volume":"41","author":"Bergonti","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1161\/CIRCULATIONAHA.119.043931","article-title":"Evidence From Family Studies for Autoimmunity in Arrhythmogenic Right Ventricular Cardiomyopathy: Associations of Circulating Anti-Heart and Anti-Intercalated Disk Autoantibodies With Disease Severity and Family History","volume":"141","author":"Caforio","year":"2020","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/ejhf.2496","article-title":"Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: Negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies","volume":"24","author":"Baritussio","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Caforio, A.L.P., De Luca, G., Baritussio, A., Seguso, M., Gallo, N., Bison, E., Cattini, M.G., Pontara, E., Gargani, L., and Pepe, A. (2021). Serum Organ-Specific Anti-Heart and Anti-Intercalated Disk Autoantibodies as New Autoimmune Markers of Cardiac Involvement in Systemic Sclerosis: Frequency, Clinical and Prognostic Correlates. Diagnostics, 11.","DOI":"10.3390\/diagnostics11112165"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Caforio, A.L.P., Baritussio, A., Marcolongo, R., Cheng, C.-Y., Pontara, E., Bison, E., Cattini, M.G., Gallo, N., Plebani, M., and Iliceto, S. (2021). Serum Anti-Heart and Anti-Intercalated Disk Autoantibodies: Novel Autoimmune Markers in Cardiac Sarcoidosis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10112476"},{"key":"ref_20","first-page":"132571","article-title":"Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy\/Dysplasia","volume":"418","author":"Marcus","year":"2010","journal-title":"Circulation"},{"key":"ref_21","first-page":"euab116.539","article-title":"Anti-desmoglein2 autoantibodies are present in patients with cardiac sarcoidosis and correlate with cardiac inflammation","volume":"23","author":"Suna","year":"2021","journal-title":"EP Eur."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Obuchowski, N.A., and Bullen, J.A. (2018). Receiver operating characteristic (ROC) curves: Review of methods with applications in diagnostic medicine. Phys. Med. Biol., 63.","DOI":"10.1088\/1361-6560\/aab4b1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-cellbio-100913-013212","article-title":"Cadherin adhesion and mechanotransduction","volume":"30","author":"Leckband","year":"2014","journal-title":"Annu. Rev. Cell. Dev. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/08916930310001657010","article-title":"Diagnostic Accuracy of Elisa Methods as an Alternative Screening Test to Indirect Immunofluorescence for the Detection of Antinuclear Antibodies. Evaluation of Five Commercial Kits","volume":"37","author":"Tonutti","year":"2004","journal-title":"Autoimmunity"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Matson, R.S. (2023). Screening for Antibody Specificity and Sensitivity with ELISA. ELISA: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-0716-2903-1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1084\/jem.181.6.1945","article-title":"How can cryptic epitopes trigger autoimmunity?","volume":"181","author":"Lanzavecchia","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Xu, Z., Zhu, W., Wang, C., Huang, L., Zhou, Q., Hu, J., Cheng, X., and Hong, K. (2017). Genotype-phenotype relationship in patients with arrhythmogenic right ventricular cardiomyopathy caused by desmosomal gene mutations: A systematic review and meta-analysis. Sci. Rep., 7.","DOI":"10.1038\/srep41387"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/hrt.2009.187138","article-title":"Anti-heart and anti-intercalated disk autoantibodies: Evidence for autoimmunity in idiopathic recurrent acute pericarditis","volume":"96","author":"Caforio","year":"2010","journal-title":"Heart"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1006\/bbrc.1999.0761","article-title":"Subclass specificity of autoantibodies against myosin in patients with idiopathic dilated cardiomyopathy: Pro-inflammatory antibodies in DCM patients","volume":"259","author":"Warraich","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rubino, M., Scatteia, A., Frisso, G., Pacileo, G., Caiazza, M., Pascale, C.E., Guarini, P., Limongelli, G., and Dellegrottaglie, S. (2021). Imaging the \u201cHot Phase\u201d of a Familiar Left-Dominant Arrhythmogenic Cardiomyopathy. Genes, 12.","DOI":"10.3390\/genes12121933"},{"key":"ref_31","first-page":"e013046","article-title":"Acute Isolated Right Ventricular Myocarditis","volume":"14","author":"Laissy","year":"2021","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1093\/eurheartj\/ehad194","article-title":"2023 ESC Guidelines for the management of cardiomyopathies: Developed by the task force on the management of cardiomyopathies of the European Society of Cardiology (ESC)","volume":"44","author":"Arbelo","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1253\/circj.CJ-08-1151","article-title":"Autoimmune Mechanisms Underlying Dilated Cardiomyopathy","volume":"73","author":"Yoshikawa","year":"2009","journal-title":"Circ. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/ejhf.3220","article-title":"Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study","volume":"26","author":"Caforio","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00392-016-1011-z","article-title":"Long-term outcome of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy after immunosuppressive therapy","volume":"105","author":"Escher","year":"2016","journal-title":"Clin. Res. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.yjmcc.2022.06.006","article-title":"High frequency of anti-DSG 2 antibodies in post COVID-19 serum samples","volume":"170","author":"Lee","year":"2022","journal-title":"J. Mol. Cell. Cardiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/22\/6736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:28:59Z","timestamp":1760113739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/22\/6736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":36,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["jcm13226736"],"URL":"https:\/\/doi.org\/10.3390\/jcm13226736","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]}}}