Evidence for autoimmunity to myosin and other heart-specific autoantigens in patients with dilated cardiomyopathy and their relatives

ALP Caforioa, JH Goldman, AJ Haven, KM Baig… - International journal of …, 1996 - Elsevier
ALP Caforioa, JH Goldman, AJ Haven, KM Baig, WJ McKenna
International journal of cardiology, 1996Elsevier
Autoimmune disease is characterised by the presence of 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 diseased
target organ. At least in a patient subset, myocarditis and dilated cardiomyopathy (DCM) …
Autoimmune disease is characterised by the presence of 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 diseased target 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 disease of 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 immunofluorescence and 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 autoantibodies detected by immunofluorescence are directed against multiple antigens. One of these, first identified using immunoblotting and confirmed by ELISA, is the cardiac-specific α-myosin isoform. 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, α-myosin is entirely cardiac-specific and is only expressed in the myocardium. Using ELISA, high titer organ- and disease-specific anti α-myosin antibodies have been found in 16% of the symptom-free relatives of DCM patients and in 38% of the pedigrees of the same cohort of relatives studied by immunofluorescence. The ELISA results provide additional evidence for autoimmunity in a subset of DCM families, and emphasise the importance of α-myosin as a target antigen.
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