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
Alida Linda Patrizia Caforio,
Giacomo De Luca,
Anna Baritussio,
Mara Seguso,
Nicoletta Gallo,
Elisa Bison,
Maria Grazia Cattini,
Elena Pontara,
Luna Gargani,
Alessia Pepe,
Corrado Campochiaro,
Mario Plebani,
Sabino Iliceto,
Giovanni Peretto,
Antonio Esposito,
Lorenzo Tofani,
Alberto Moggi-Pignone,
Lorenzo Dagna,
Renzo Marcolongo,
Marco Matucci-Cerinic,
Cosimo Bruni
Affiliations
Alida Linda Patrizia Caforio
Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy
Giacomo De Luca
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
Anna Baritussio
Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy
Mara Seguso
Department of Laboratory Medicine, University of Padua, 35122 Padua, Italy
Nicoletta Gallo
Department of Laboratory Medicine, University of Padua, 35122 Padua, Italy
Elisa Bison
Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy
Maria Grazia Cattini
Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy
Elena Pontara
Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy
Luna Gargani
Institute of Clinical Physiology, National Council of Research, 56124 Pisa, Italy
Alessia Pepe
Department of Medicine, Institute of Radiology, University of Padova, 35122 Padova, Italy
Corrado Campochiaro
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
Mario Plebani
Department of Laboratory Medicine, University of Padua, 35122 Padua, Italy
Sabino Iliceto
Cardiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35122 Padua, Italy
Giovanni Peretto
Unit of Arrhythmology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
Antonio Esposito
Clinical and Experimental Radiology Unit, Expirimental Imaging Center, IRCCS San Raffaele Scientific Institute, Ospedale San Raffaele University, 20132 Milan, Italy
Lorenzo Tofani
Division of Rheumatology, Department of Experimental and Clinical Medicine, Department of Geriatric Medicine AOUC, University of Florence, 50121 Florence, Italy
Alberto Moggi-Pignone
Division of Internal Medicine Unit IV AOUC, Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy
Lorenzo Dagna
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
Renzo Marcolongo
Haematology and Clinical Immunology, Department of Medicine, University of Padua, 35122 Padua, Italy
Marco Matucci-Cerinic
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
Cosimo Bruni
Division of Rheumatology, Department of Experimental and Clinical Medicine, Department of Geriatric Medicine AOUC, University of Florence, 50121 Florence, Italy
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 ± 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 p 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.
