{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T08:26:32Z","timestamp":1784967992574,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts of AHA and AIDA in SSc. Methods: The study included consecutive SSc patients (n = 116, aged 53 \u00b1 13 years, 83.6% females, median disease duration 7 years) with clinically suspected heart involvement (symptoms, abnormal ECG, abnormal troponin I or natriuretic peptides, and abnormal echocardiography). All SSc patients underwent CMR. Serum AHA and AIDA were measured by indirect immunofluorescence in SSc and in control groups of non-inflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141), and normal blood donors (NBD) (n = 270). AHA and AIDA status in SSc was correlated with baseline clinical, diagnostic features, and outcome. Results: The frequency of AHA was higher in SSc (57\/116, 49%, p &lt; 0.00001) than in NICD (2\/160, 1%), IHF (2\/141, 1%), or NBD (7\/270, 2.5%). The frequency of AIDA was higher (65\/116, 56%, p &lt; 0.00001) in SSc than in NICD (6\/160, 3.75%), IHF (3\/141, 2%), or NBD (1\/270, 0.37%). AHAs were associated with interstitial lung disease (p = 0.04), history of chest pain (p = 0.026), abnormal troponin (p = 0.006), AIDA (p = 0.000), and current immunosuppression (p = 0.01). AHAs were associated with death (p = 0.02) and overall cardiac events during follow-up (p = 0.017). Conclusions: The high frequencies of AHA and AIDA suggest a high burden of underdiagnosed autoimmune HInv in SSc. In keeping with the negative prognostic impact of HInv in SSc, AHAs were associated with dismal prognosis.<\/jats:p>","DOI":"10.3390\/diagnostics11112165","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T02:55:17Z","timestamp":1637636117000},"page":"2165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["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"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-5655","authenticated-orcid":false,"given":"Alida Linda Patrizia","family":"Caforio","sequence":"first","affiliation":[{"name":"Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"De Luca","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-6705","authenticated-orcid":false,"given":"Anna","family":"Baritussio","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Seguso","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-5382","authenticated-orcid":false,"given":"Elisa","family":"Bison","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-2661","authenticated-orcid":false,"given":"Maria Grazia","family":"Cattini","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-7081","authenticated-orcid":false,"given":"Elena","family":"Pontara","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-453X","authenticated-orcid":false,"given":"Luna","family":"Gargani","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Pepe","sequence":"additional","affiliation":[{"name":"Department of Medicine, Institute of Radiology, University of Padova, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-3794","authenticated-orcid":false,"given":"Corrado","family":"Campochiaro","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Plebani","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabino","family":"Iliceto","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-4000","authenticated-orcid":false,"given":"Giovanni","family":"Peretto","sequence":"additional","affiliation":[{"name":"Unit of Arrhythmology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Esposito","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Radiology Unit, Expirimental Imaging Center, IRCCS San Raffaele Scientific Institute, Ospedale San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9965-7667","authenticated-orcid":false,"given":"Lorenzo","family":"Tofani","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Experimental and Clinical Medicine, Department of Geriatric Medicine AOUC, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Moggi-Pignone","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine Unit IV AOUC, Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Dagna","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Marcolongo","sequence":"additional","affiliation":[{"name":"Haematology and Clinical Immunology, Department of Medicine, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Matucci-Cerinic","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Division of Rheumatology, Department of Experimental and Clinical Medicine, Department of Geriatric Medicine AOUC, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-2083","authenticated-orcid":false,"given":"Cosimo","family":"Bruni","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Experimental and Clinical Medicine, Department of Geriatric Medicine AOUC, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/2397198317747441","article-title":"Update on assessment and management of primary cardiac involvement in systemic sclerosis","volume":"3","author":"Bournia","year":"2018","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/2397198320924873","article-title":"Overall mortality","volume":"6","author":"Moore","year":"2020","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101668","DOI":"10.1016\/j.berh.2021.101668","article-title":"Cardiac involvement in systemic sclerosis: Getting to the heart of the matter","volume":"35","author":"Bruni","year":"2021","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bruni, C., Buch, M.H., Furst, D.E., De Luca, G., Djokovic, A., Dumitru, R.B., Giollo, A., Polovina, M., Steelandt, A., and Bratis, K. (2021). Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF\/HFA definition. J. Scleroderma Relat. Disord.","DOI":"10.1177\/23971983211053246"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1093\/rheumatology\/kez494","article-title":"Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS)","volume":"59","author":"Mavrogeni","year":"2020","journal-title":"Rheumatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/0002-8703(93)90075-K","article-title":"Cardiac and skeletal muscle disease in systemic sclerosis (scleroderma): A high risk association","volume":"125","author":"Follansbee","year":"1993","journal-title":"Am. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/art.38942","article-title":"Cardiomyopathy in murine models of systemic sclerosis","volume":"67","author":"Venalis","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5301\/jsrd.5000249","article-title":"Pathogenesis of systemic sclerosis: Recent insights of molecular and cellular mechanisms and therapeutic opportunities","volume":"2","author":"Varga","year":"2017","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mueller, K.A., Mueller, I.I., Eppler, D., Zuern, C.S., Seizer, P., Kramer, U., Koetter, I., Roecken, M., Kandolf, R., and Gawaz, M. (2015). Clinical and histopathological features of patients with systemic sclerosis undergoing endomyocardial biopsy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126707"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.semarthrit.2013.07.006","article-title":"Recognizing and treating myocarditis in recent-onset systemic sclerosis heart disease: Potential utility of immunosuppressive therapy in cardiac damage progression","volume":"43","author":"Pieroni","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1093\/rheumatology\/kez658","article-title":"Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: A comparative histological analysis","volume":"59","author":"Campochiaro","year":"2020","journal-title":"Rheumatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1093\/eurheartj\/ehx321","article-title":"Diagnosis and management of myocardial involvement in systemic immune-mediated diseases: A position statement of the ESC Working Group on Myocardial and Pericardial Disease","volume":"38","author":"Caforio","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ijcard.2018.11.104","article-title":"Impact of systemic immune-mediated diseases on clinical features and prognosis of patients with biopsy-proved myocarditis","volume":"280","author":"Peretto","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ejim.2018.10.013","article-title":"Cardiac troponin T and NT-proBNP as diagnostic and prognostic biomarkers of primary cardiac involvement and disease severity in systemic sclerosis: A prospective study","volume":"60","author":"Bosello","year":"2019","journal-title":"Eur. J. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/ard.2008.103382","article-title":"Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis","volume":"69","author":"Allanore","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1002\/art.22971","article-title":"Pattern and distribution of myocardial fibrosis in systemic scleroderma, a delayed enhanced MRI study","volume":"56","author":"Tzelepis","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1136\/ard.2008.095836","article-title":"Cardiac magnetic resonance imaging in systemic sclerosis: A cross-sectional observational study of 52 patients","volume":"68","author":"Hachulla","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jcmg.2018.09.025","article-title":"Early Detection of Cardiac Involvement in Systemic Sclerosis: The Added Value of Magnetic Resonance Imaging","volume":"12","author":"Gargani","year":"2019","journal-title":"JACC Cardiovasc. Imaging."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1093\/rheumatology\/ket002","article-title":"Early detection of myocardial and pulmonary oedema with MRI in an asymptomatic systemic sclerosis patient: Successful recovery with pulse steroid","volume":"52","author":"Pingitore","year":"2013","journal-title":"Rheumatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/0735-1097(90)92821-I","article-title":"Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy","volume":"15","author":"Caforio","year":"1990","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1161\/CIRCULATIONAHA.106.641472","article-title":"Prospective Familial Assessment in Dilated Cardiomyopathy","volume":"115","author":"Caforio","year":"2007","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1093\/eurheartj\/ehm076","article-title":"A prospective study of biopsy-proven myocarditis: Prognostic relevance of clinical and aetiopathogenetic features at diagnosis","volume":"28","author":"Caforio","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.jacep.2020.05.013","article-title":"Immunosuppressive Therapy and Risk Stratification of Patients With Myocarditis Presenting With Ventricular Arrhythmias","volume":"6","author":"Peretto","year":"2020","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1136\/annrheumdis-2013-203716","article-title":"Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: Evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis","volume":"73","author":"Minier","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/art.38098","article-title":"2013 classification criteria for systemic sclerosis: An American College of Rheumatology\/European League against Rheumatism collaborative initiative","volume":"65","author":"Khanna","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_28","first-page":"1573","article-title":"Criteria for the classification of early systemic sclerosis","volume":"28","author":"LeRoy","year":"2001","journal-title":"J. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ruaro, B., Nallino, M.G., Casabella, A., Salton, F., Confalonieri, P., De Tanti, A., and Bruni, C. (2020). Monitoring the microcirculation in the diagnosis and follow-up of systemic sclerosis patients: Focus on pulmonary and peripheral vascular manifestations. Microcirculation, 27.","DOI":"10.1111\/micc.12647"},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","article-title":"2015 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"37","author":"Humbert","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/eji.202048930","article-title":"Anti-heart antibodies levels and their correlation with clinical symptoms and outcomes in patients with confirmed or suspected diagnosis COVID-19","volume":"51","author":"Blagova","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ijcard.2014.10.165","article-title":"Passive Transfer of Affinity-Purified Anti-Heart Autoantibodies (AHA) from Sera of Patients with Myocarditis Induces Experimental Myocarditis in Mice","volume":"179","author":"Caforio","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1161\/01.CIR.85.5.1734","article-title":"Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy","volume":"85","author":"Caforio","year":"1992","journal-title":"Circulation"},{"key":"ref_35","first-page":"25","article-title":"Smoking and systemic sclerosis: Influence on microangiopathy and expression of anti-topoisomerase I antibodies in a monocentric cohort","volume":"38","author":"Ciaffi","year":"2020","journal-title":"Clin. Exp. Rheumatol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:34:12Z","timestamp":1760168052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,22]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["diagnostics11112165"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11112165","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,22]]}}}