Beta-adrenoceptor antibodies and genetics in dilated cardiomyopathy--an overview and review.
Autoantibodies against the cardiac beta-adrenoceptor are present in 30-40% of patients with idiopathic dilated cardiomyopathy and can be detected using ligand binding inhibition, immunoprecipitation or immunoblotting. The functional consequences of the antibody-receptor interactions are two-fold: (a) in isolated cardiac myocytes, diluted sera from cardiomyopathy patients induce internalization of the beta-receptors which are subsequently degraded intracellularly; (b) in membrane preparations, anti-receptor antibodies inhibit selectively the activity of isoproterenol-sensitive adenylate cyclase. The presence of anti-receptor antibodies is strongly linked to the HLA-DR4 phenotype: 72% of the HLA-DR4 patients in our series had anti-beta-receptor antibodies compared with 22% of the HLA-DR4-negative patients (most of which typed as HLA-DR1). Conversely, 67% of the antibody-positive patients typed as HLA-DR4, compared with only 10% of the antibody-negative patients. These results indicate the presence, in a subset of cardiomyopathy patients, of immunogenetical factors which may modulate myocardial beta-adrenoceptor function.
Limas
C J
CJ
Department of Medicine (Cardiovascular Division), University of Minnesota School of Medicine, Minneapolis 55455.
Limas
C
C
D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000276:immunology*; D008040:Genetic Linkage; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D009206:Myocardium / Q000276:immunology; D011943:Receptors, Adrenergic, beta / Q000276:immunology*
D001323:Autoantibodies; D015804:HLA-DR4 Antigen; D011943:Receptors, Adrenergic, beta