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

Abstract

We investigated whether autoantibodies against the human beta-adrenergic receptor (beta-AR) might be involved in cardiomyopathies secondary to valvular heart disease (VHD) or hypertensive heart disease (HHD). Autoimmunity to beta-AR has been proposed as a pathogenic principle in human cardiomyopathy. Recently, by the use of intact recombinant human beta-AR, we were able to confirm the existence of functionally active anti-beta-1-AR autoantibodies in patients with dilated cardiomyopathy (26% prevalence) or ischemic cardiomyopathy (10% prevalence); however, their prevalence in other (secondary) cardiomyopathies remained to be determined. Immunoglobulin G (IgG) was prepared from the sera of 28 VHD and 19 HHD patients and first screened by a peptide-based enzyme-linked immunosorbent assay (antigens: aminoterminus, second extracellular loop [ECII] and carboxyterminus of human beta-1- and beta-2-AR). IgG from 108 gender- and age-matched healthy subjects served to define the threshold for positive immunoreactions. Positive sera were further screened for their ability to recognize and activate native human beta-AR situated in a cell membrane. Twenty-five percent (VHD) or 11% (HHD) of the patients and 4% of the healthy controls had IgG antibodies randomly directed against all the three domains tested and both beta-AR subtypes. Only one patient with aortic valve and concomitant coronary heart disease and one healthy subject had functionally active anti-b1-AR (targeting beta-1-ECII). Moreover, one HHD patient with concomitant collagenosis had IgG that was cross-reacting with recombinant beta-AR in immunological assays but was unable to affect receptor function. Autoimmune reactions against the human beta-AR do not appear to be associated with cardiomyopathies secondary to VHD or HHD.