ELSEVIER International Journal of Cardiology 54 (1996) 157-163 International Journal of cardiology Evidence for autoimmunity to myosin and other heart-specific autoantigens in patients with dilated cardiomyopathy and their relatives Alida L.P. CaforioaTb’*, Jonathan H. Goldman”, Aldwyn J. Haven”, Kamran M. Baig”, William J. McKennaa “Department of Cardiological Sciences, St George ‘s Hospital Medical School, Cranmer Terrace, London SW1 7 ORE, UK bInstitute of Clinical Medicine, Division of Cardiology, University of Padua, Padua. Italy Abstract Autoimmune diseaseis characterisedby the presenceof circulating autoantibodies in the affected patients and in a proportion of their relatives. These antibodies are generally not pathogenic but are reliable markers of immune-mediated tissue damage.In organ-specific autoimmune disease,the destruction process is largely restricted to one organ within the body and the autoantibodies react with autoantigens which are unique to the diseasedtarget organ. At least in a patient subset, myocarditis and dilated cardiomyopathy (DCM) may represent the acute and chronic stages of a progressive organ-specific autoimmune diseaseof the myocardium. Autoimmune features in patients with myocarditis/DCM include: familial aggregation, a weak association with HLA-DR4, abnormal expression of HLA class II on cardiac endothelium on endomyocardial biopsy, and detection of organ- and disease-specific cardiac autoantibodies, by immunofluorescenceand absorption techniques, in the affected patients and in a proportion of their symptom-free relatives from both familial and non-familial DCM pedigrees. The organ-specific cardiac autoantibodiesdetected by immunofluorescence are directed against multiple antigens. One of these, first identified using immunoblotting and confirmed by ELISA, is the cardiac-specific cu-myosinisoform. Myosin fulfils the expected criteria for organ-specific autoimmunity, in that immunisation with cardiac but not skeletal myosin reproduces, in susceptible mouse strains, the human disease phenotype of DCM; in addition, cu-myosin is entirely cardiac-specific and is only expressed in the myocardium. Using ELISA, high titer organ- and disease-specific anti a-myosin antibodies have been found in 16% of the symptom-free relatives of DCM patients and in 38% of the pedigreesof the samecohort of relatives studied by immunofluorescence. The ELISA results provide additional evidence for autoimmunity in a subset of DCM families, and emphasise the importance of cY-myosin as a target antigen. Keywords: Dilated cardiomyopathy; Familial; Autoimmunity; Autoantibodies; Myosin; Immunology 1. Introduction Dilated cardiomyopathy (DCM) is a chronic heart muscle disease of unknown cause that is character- *Corresponding author at London address. Tel.: +44 181 725 5911; fax: +44 181 682 0944. ised by dilatation and contractile dysfunction of the left and/or the right ventricle [l]. It is a major cause of severe heart failure in young people and the commonest indication for transplantation world-wide [2,3]. Despite recent improvements in clinical man- agement, prognosis remains poor with 40-50% of patients dying within 2 years after diagnosis [2]. The 0167-5273/96/$15,00 0 1996 Elsevier Science Ireland Ltd. All rights reserved PII SO167-5273(96)02593-4