AUTOANTIBODIES AGAINST CARDIAC G-PROTEIN-COUPLED RECEPTORS DEFINE DIFFERENT POPULATIONS WITH CARDIOMYOPATHIES BUT NOT WITH HYPERTENSION

It was previously shown that the second extracellular loop of cardiova scular G-protein-coupled receptors is an antigenic target for pharmaco logically active autoantibodies in patients with idiopathic dilated ca rdiomyopathy. To extend these observations to cover patients with the same disease from different geographical origins or to patients with o ther cardiac diseases, peptides corresponding to the sequences of the second extracellular loops of the human M2 muscarinic receptors and be ta adrenoceptors were used as antigens in an enzyme immunoassay. Sera from patients from Sweden and Japan with idiopathic dilated cardiomyop athy (DCM, n = 32), hypertrophic cardiomyopathy (HCM, n = 23), maligna nt essential hypertension (MEH, n = 11), malignant secondary hypertens ion (MSH, n = 10), and sera from healthy blood donors (HBD, n = 49) we re tested. Sera from patients with DCM recognized the muscarinic recep tor peptide in 38% of cases and the beta 1 adrenoceptor peptide in 31% of cases. In 50% of the positive patients, autoantibodies against bot h peptides coexisted as shown by competition experiments using both pe ptides as inhibitors. In HCM patients, there was a lower frequency of autoantibodies but with a higher but not significant predominance agai nst the M2 peptide. No autoantibodies were detected in sera from patie nts with MEH or MSH. Autoantibodies against the M2 muscarinic receptor s, affinity-purified from positive patients, displayed pharmacological activity as demonstrated by changes in the affinity and number of rad ioligand binding sites. In contrast, antibodies purified from positive HBD had no effect. These results confirm that autoantibodies displayi ng pharmacological activity against G-protein-coupled cardiovascular r eceptors are mainly restricted to patients with idiopathic dilated car diomyopathy and that different autoantibody populations are responsibl e for the recognition of the different receptors. (C) 1994 Academic Pr ess, Inc.