Anti-β-adrenoceptors autoimmunity causing 'idiopathic' arrhythmias and cardiomyopathy

Background: To determine the prevalence of anti-β-adrenoceptors autoantibodies (aβAA) in patients with idiopathic arrhythmias (IA) and to assess whether aβAA are predictive markers for concealed cardiomyopathy in such patients. Methods and Results: Sixty-seven patients (group 1) with IA [25 supraventricular (SVA) and 42 ventricular (VA)]; 14 patients (group 2) with suspected cardiomyopathy, 12 patients with definite cardiomyopathy (group 3); and 19 healthy controls (group 4) were tested with an enzyme immunoassay, using synthetic peptides corresponding to the second extracellular loop of the human β1- and β2-adrenoceptors. Endomyocardial biopsy was performed in 29 patients. As compared with group 4 [3/19 (15.7%)], anti-β1-adrenoceptor autoantibodies (aβ1AA) were more frequent in group-1 patients [38/67 (56.7%; P<0.01): 27/42 (64.2%; P<0.001) with VA and 11/25 (44%; P<0.05) with SVA]. 3 of the group 1 patients also had anti-β2-adrenoceptor autoantibodies (aβ2AA). 4 were positive for aβ2AA only. Biopsy performed in 11/67 group 1 patients was abnormal in all. Of them, 7/8 (87.5%) with VA and 3/3 (100%) with SVA were positive for aβ1AA. PCR analysis from paraffin blocks of the 11 group 1 biopsied patients was negative for EV, EBV, HCV, AV, PVB19, INF A/B,HSV1/2, HHV6 and HHV8 viral genomes. Conclusions: The second extracellular loop of the β-adrenoceptor is the molecular target of specific autoantibodies. Positivity for aβ1AA predicts abnormal histological findings in 90% of IA patients and suggests that autoimmunity might play an arrhythmogenic role.