Аннотация
OBJECTIVES: 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). BACKGROUND: 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. 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
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. RESULTS: 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. CONCLUSIONS: Autoimmune reactions against
the human beta-AR do not appear to be associated with cardiomyopathies
secondary to VHD or HHD.
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