This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jahns, R. Articles by Inselmann, G. Search for Related Content PubMed PubMed Citation Articles by Jahns, R. Articles by Inselmann, G.

CLINICAL STUDIES

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

Roland Jahns, MD^*, Valérie Boivin, PhD, Christian Siegmund, MD, Fritz Boege, MD^*, Martin J. Lohse, MD and Gerhard Inselmann, MD^*

^* Department of Internal Medicine, Medizinische Poliklinik, University of Wuerzburg, Wuerzburg, Germany
Department of Pharmacology, University of Wuerzburg, Wuerzburg, Germany

Manuscript received November 3, 1998; revised manuscript received May 12, 1999, accepted June 29, 1999.

Reprint requests and correspondence: Dr. Roland Jahns, Medizinische Poliklinik der Universität Wuerzburg, Klinikstraße 6-8, D-97070 Wuerzburg, Germany
jahns{at}wpxx02.toxi.uni-wuerzburg.de

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.

Abbreviations and Acronyms   anti-beta-1-AR/-ECII = antibodies against the beta-1-adrenergic receptor/second extracellular loop of the beta-1-adrenergic receptor   beta-AR = beta-adrenergic receptor   BSA = bovine serum albumin   DCM = dilated cardiomyopathy   ELISA = enzyme-linked immunoabsorbent assay   HHD = hypertensive heart disease   HPLC = high-performance liquid chromatography   ICM = ischemic cardiomyopathy   IgG = immunoglobulin G   PBS = phosphate-buffered saline   VHD = valvular heart disease

This article has been cited by other articles:

				A. S. Tutor, P. Penela, and F. Mayor Jr. Anti-{beta}1-adrenergic receptor autoantibodies are potent stimulators of the ERK1/2 pathway in cardiac cells Cardiovasc Res, October 1, 2007; 76(1): 51 - 60. [Abstract] [Full Text] [PDF]

				V. O. Nikolaev, V. Boivin, S. Stork, C. E. Angermann, G. Ertl, M. J. Lohse, and R. Jahns A Novel Fluorescence Method for the Rapid Detection of Functional {beta}1-Adrenergic Receptor Autoantibodies in Heart Failure J. Am. Coll. Cardiol., July 31, 2007; 50(5): 423 - 431. [Abstract] [Full Text] [PDF]

				A. M. Feldman and D. McNamara Myocarditis N. Engl. J. Med., November 9, 2000; 343(19): 1388 - 1398. [Full Text] [PDF]

				R. Jahns, V. Boivin, T. Krapf, G. Wallukat, F. Boege, and M. J. Lohse Modulation of beta1-adrenoceptor activity by domain-specific antibodies and heart failure-associated autoantibodies J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1280 - 1287. [Abstract] [Full Text] [PDF]