Localization of a Functional Autoimmune Epitope on the Muscarinic Acetylcholine Receptor-2 in Patients with Idiopathic Dilated Cardiomyopathy

A peptide corresponding to the sequence 169-193 ofthe second extracellular loop of the human muscarinic acetylcholine re-ceptor-2 was used as an antigen to screen sera from patients with idiopathic dilated cardiomyopathy (DCM, n = 36) and healthy blood donors (HBD, n = 40). The sera from 14 pa-tients with DCM (38.8%) and 3 HBD (7.5%) recognized the muscarinic receptor peptide at dilutions varying from 1:20 to 1:160 in ELISA. A highly significant correlation (P = 0.006) was found between the presence of antimuscarinic receptor-2 autoantibodies and anti-fl-adrenoceptor-1 autoantibodies in the patients ' sera. Affinity-purified autoantibodies from positive sera of patients with DCM recognized on the electrotransferred protein of rat ventricular membrane a major band of about 80 kD. Incubation of autoantibodies with membrane resulted not only in a decrease in the maximal binding sites (B..) but also in an increase in Kd of radioligand binding in a concentration-de-pendent manner. This suggests a mixed-type of inhibition. Moreover, preincubation with atropine abolished the inhibitory effect of autoantibodies on the receptor binding whereas carba-chol appeared to have no effect on the activity of the autoanti-bodies. These data define a subgroup of patients with idiopathic DCM who have in their sera functionally active autoantibodies against muscarinic receptor-2. (J. Clin. Invest. 1993.91:1964-1968.) Key words: muscarinic receptor * autoimmunity * epitope mapping. dilated cardiomyopath