Mapping of a functional autoimmune epitope on the beta 1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy.
The presence and properties of serum autoantibodies against beta-adrenergic receptors in patients with idiopathic dilated cardiomyopathy were studied using synthetic peptides derived from the predicted sequences of the human beta-adrenergic receptors. Peptides corresponding to the sequences of the second extracellular loop of the human beta 1- and beta 2-adrenergic receptors were used as antigens in an enzyme immunoassay to screen sera from patients with dilated cardiomyopathy (n = 42), ischemic heart disease (n = 17), or healthy blood donors (n = 34). The sera of thirteen dilated cardiomyopathy patients, none of the ischemic heart disease patients, and four of the healthy controls monospecifically recognized the beta 1-peptide. Only affinity-purified antibodies of these patients had a inhibitory effect on radioligand binding to the beta 1 receptor of C6 rat glioma cells. They recognized the receptor protein by immunoblot and bound in situ to human myocardial tissue. We conclude that a subgroup of patients with idiopathic dilated cardiomyopathy have in their sera autoantibodies specifically directed against the second extracellular loop of the beta 1-adrenergic receptor. These antibodies could serve as a marker of an autoimmune response with physiological and/or pathological implications.
Wallenberg Laboratory, Division of Cardiology, Göteborg, Sweden.
Y
Y
Magnusson
S
S
Marullo
S
S
Hoyer
F
F
Waagstein
B
B
Andersson
A
A
Vahlne
J G
JG
Guillet
A D
AD
Strosberg
A
A
Hjalmarson
J
J
Hoebeke
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D011943:Receptors, Adrenergic, beta