MAPPING OF A FUNCTIONAL AUTOIMMUNE EPITOPE ON THE BETA-1-ADRENERGIC RECEPTOR IN PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY

The presence and properties of serum autoantibodies against β-adrenergic receptors in patients with idiopathic dilated cardiomyopathy were studied using synthetic peptides derived from the predicted sequences of the human β-adrenergic receptors. Peptides corresponding to the sequences of the second extracellular loop of the human β1- and β2-adrenergic receptors were used as antigens in an enzyme immunoassay to screen sera from patients with dilated cardiomyopathy (n = 42), ischemic heart disease (n = 17), or healthy blood donors (n = 34). The sera of thirteen dilated cardiomyopathy patients, none of the ischemic heart disease patients, and four of the healthy controls monospecifically recognized the β1-peptide. Only affinity-purified antibodies of these patients had a inhibitory effect on radioligand binding to the β1 receptor of C6 rat glioma cells. They recognized the receptor protein by immunoblot and bound in situ to human myocardial tissue. We conclude that a subgroup of patients with idiopathic dilated cardiomyopathy have in their sera autoantibodies specifically directed against the second extracellular loop of the β1-adrenergic receptor. These antibodies could serve as a marker of an autoimmune response with physiological and/or pathological implications.