Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction.
BACKGROUND
The relationship between anti-beta-adrenergic (anti-betaR) and anti-M(2)-cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated.


RESULTS
We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas' heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas' heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-beta(1)RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for beta(1),beta(2)-adrenergic receptors (cAMP increment) or M(2)-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-betaRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-betaRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol.


CONCLUSIONS
Our results demonstrate a strong correlation between anti-betaRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-betaRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.
Division of Cardiology, Ramos Mejía Hospital and Institute of Genetic Engineering and Molecular Biology (INGEBI-CONICET), Buenos Aires, Argentina. pchiale@sinectis.com.ar
P A
PA
Chiale
I
I
Ferrari
E
E
Mahler
M A
MA
Vallazza
M V
MV
Elizari
M B
MB
Rosenbaum
M J
MJ
Levin
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001146:Arrhythmia, Sinus / Q000150:complications / Q000276:immunology*; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000276:immunology*; D001285:Atropine / Q000494:pharmacology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D019556:COS Cells; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000150:complications / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015290:Second Messenger Systems / Q000187:drug effects
D001323:Autoantibodies; D007074:Immunoglobulin G; D010716:Phosphatidylinositols; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D001285:Atropine; D011433:Propranolol; D000242:Cyclic AMP