Activating beta-1-adrenoceptor antibodies are not associated with cardiomyopathies secondary to valvular or hypertensive heart disease

OBJECTIVES We investigated whether autoantibodies against the human beta-ad renergic receptor (beta-AR) might be involved in cardiomyopathies secondary to valvular heart disease (VHD) or hypertensive heart disease (HHD). BACKGROUND Autoimmunity to beta-AR has been proposed as a pathogenic princi ple in human cardiomyopathy. Recently, by the use of intact recombinant hum an beta-AR, we were able to confirm the existence of functionally active an ti-beta-1-AR autoantibodies in patients with dilated cardiomyopathy (26% pr evalence) or ischemic cardiomyopathy (10% prevalence); however, their preva lence in other (secondary) cardiomyopathies remained to be determined. METHODS Immunoglobulin G (IgG) was prepared from the sera of 28 VHD and 19 HHD patients and first screened by a peptide-based enzyme-linked immunosorb ent assay (antigens: aminoter-minus, second extracellular loop [ECII] and c arboxyterminus of human beta-1- and beta-2-AR). IgG from 108 gender- and ag e-matched healthy subjects served to define the threshold for positive immu noreactions. Positive sera were further screened for their ability to recog nize and activate native human beta-AR situated in a cell membrane. RESULTS Twenty-five percent (VHD) or 11% (HHD) of the patients and 4% of th e healthy controls had IgG antibodies randomly directed against all the thr ee domains tested and both beta-AR subtypes. Only one patient with aortic v alve and concomitant coronary heart disease and one healthy subject had fun ctionally active anti-bl-AR (targeting beta-1-ECII). Moreover, one HHD pati ent with concomitant collagenosis had IgG that was cross-reacting with reco mbinant beta-AR in immunological assays but was unable to affect receptor f unction. CONCLUSIONS Autoimmune reactions against the human beta-AR do not appear to be associated with cardiomyopathies secondary to VHD or HHD. (C) 1999 by t he American College of Cardiology.