High Prevalence of Antibeta Adrenergic Receptor Antibodies with Agonist-Like Activity in Ischemic Heart Disease with Severe Left Ventricular Dysfunction

pp 151-158

Abstract

Anti β-adrenergic antibodies with agonist like properties have been reported to occur in idiopathic dilated cardiomyopathy, acute myocarditis, Chagas disease and primary ventricular arrhythmias. The actual prevalence of anti (3-adrenergic antibodies and their relationship with ventricular dysfunction in patients with ischemic heart disease is unknown. The aim or our study was to evaluate the prevalence of anti β-adrenergic anti-bodies with agonist activity in patients with is-chemic heart disease and severe left ventricular dysfunction in comparison to patients with is-chemic heart disease and midly depressed or normal ventricular function, idiopathid dilated cardiomyopathy and healthy controls. The presence of autoantibodies was assessed by an ELISA test against (31 and (32 peptides corresponding to the predicted aminoacid sequence of the second extra celular loop of the receptors in all the pa-tients sera. The functional effect of IgG from patients with ischemic heart disease and severe left ventricular dysfunction, idiopathic dilated cardiomyopathy and healthy controls as studied in cultured neonatal rat cardiomyocytes. The table summarises the results:

                   _{FE%             n                   Positive ELISA               test Positive}

                                                       _{β1       β2     β1 and β2         funct. test}

_{HC                                  10            1(10%) 1(10%) 1(10%)             0(0%)}

_{IDC            7-34 (x: 5)    14           5 (36%) 3 (21%)7 (50%)           6(43%)}

_{IHD            35-70 (x 52)  7             1(14%) 1(14%) 1(14%)              Not}

                                                                                                     _determined

_{IHD-SLVD    8-33 (x:15)   11           4(36%) 1(9%)  5(45%)           6(54%) FE: ejection fraction left ventricle. HC: healthy controls. IDC: idio-pathic dilated cardiomyopathy. IHD: ischemic heart disease. IHD-SLVD: ischemic heart disease-severe left ventricular dysfunction.}   Comparison of ELISA and functional tests revealed a significant regression coefficient in both ischemich eart disease-left severe ventricular dysfunction (r:0.875; p 0.001) and idiopathic dilated cardiomyopathy (r: 0.655; p 0.021) patients. Our results show that the sera of patients with ischemic heart disease and severe left ventricular dysfunction contain functionally active anti (3-adrenergic antibodies with a prevalence similar to that of idiopathic dilated cardiomyopathy. These findings would suggest that in patients with ischemic heart disease and severe left ventricular dysfunction the severe ischemic myocardial damage might induce an abnormal immunoregulatory response involving the R-adrenergic receptors by unknown mechanisms or, alternatively, that they could have a concomitant un-suspected myocardial disease. Demonstration of the presence of these antibodies may produce a substantial change in the current pathogenic concepts and therapeutical approaches of ischemic cardiomyopathy.