%0 Journal Article %1 Jahns1999a %A Jahns, R. %A Boivin, V. %A Siegmund, C. %A Inselmann, G. %A Lohse, M. J. %A Boege, F. %D 1999 %J Circulation %K *Antigen-Antibody Aged Autoantibodies/*immunology Cardiac Case-Control Chronic Disease Female Function, Heart/*physiopathology Humans Left/physiology Low/immunology/*physiopathology Male Middle Output, Proteins/immunology Reactions Recombinant Studies Ventricular beta-1/*immunology Receptor Adrenergic %N 5 %P 649-54 %T Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9950662 %V 99 %X BACKGROUND: Autoantibodies against synthetic peptides of beta-adrenergic receptors have been observed in human cardiomyopathy. However, it has never been shown that such antibodies really interact with native human beta-adrenergic receptors, nor has the clinical impact of such an interaction been investigated in larger groups of patients. METHODS AND RESULTS: We screened 104 patients with dilated or ischemic cardiomyopathy (NYHA functional classes II to IV) and 108 healthy subjects for IgG antibodies reacting with beta-receptor peptides. Such IgGs were further analyzed for binding and functional interactions with native recombinant human beta-adrenergic receptors. Antibodies reacting with synthetic receptor peptides were present in 51% of the patients. However, only a subgroup directed against the second extracellular receptor domain also recognized native human beta-adrenergic receptors situated in a cell membrane. All antibodies of this subgroup impaired receptor ligand binding and enhanced receptor-mediated signaling, which could be blocked by 5 micromol/L bisoprolol in vitro. Their prevalence was 1% in healthy subjects and 10% in ischemic cardiomyopathy, whereas it amounted to 26% in dilated cardiomyopathy and was associated with a significantly poorer left ventricular function. CONCLUSIONS: Our data show that activating autoantibodies against human beta-adrenergic receptors exist in approximately 25% of patients with dilated cardiomyopathy. Counteraction of such autoantibodies might contribute to the beneficial effects of beta-adrenergic receptor blockade in chronic heart failure.

@article{Jahns1999a, abstract = {BACKGROUND: Autoantibodies against synthetic peptides of beta-adrenergic receptors have been observed in human cardiomyopathy. However, it has never been shown that such antibodies really interact with native human beta-adrenergic receptors, nor has the clinical impact of such an interaction been investigated in larger groups of patients. METHODS AND RESULTS: We screened 104 patients with dilated or ischemic cardiomyopathy (NYHA functional classes II to IV) and 108 healthy subjects for IgG antibodies reacting with beta-receptor peptides. Such IgGs were further analyzed for binding and functional interactions with native recombinant human beta-adrenergic receptors. Antibodies reacting with synthetic receptor peptides were present in 51% of the patients. However, only a subgroup directed against the second extracellular receptor domain also recognized native human beta-adrenergic receptors situated in a cell membrane. All antibodies of this subgroup impaired receptor ligand binding and enhanced receptor-mediated signaling, which could be blocked by 5 micromol/L bisoprolol in vitro. Their prevalence was 1% in healthy subjects and 10% in ischemic cardiomyopathy, whereas it amounted to 26% in dilated cardiomyopathy and was associated with a significantly poorer left ventricular function. CONCLUSIONS: Our data show that activating autoantibodies against human beta-adrenergic receptors exist in approximately 25% of patients with dilated cardiomyopathy. Counteraction of such autoantibodies might contribute to the beneficial effects of beta-adrenergic receptor blockade in chronic heart failure.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Jahns, R. and Boivin, V. and Siegmund, C. and Inselmann, G. and Lohse, M. J. and Boege, F.}, biburl = {https://www.bibsonomy.org/bibtex/249f31ecfe45dcadc89afdb756dd2e22f/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {13acbc1b1852b8b68044c8568e46fba2}, intrahash = {49f31ecfe45dcadc89afdb756dd2e22f}, issn = {0009-7322 (Print) 0009-7322 (Linking)}, journal = {Circulation}, keywords = {*Antigen-Antibody Aged Autoantibodies/*immunology Cardiac Case-Control Chronic Disease Female Function, Heart/*physiopathology Humans Left/physiology Low/immunology/*physiopathology Male Middle Output, Proteins/immunology Reactions Recombinant Studies Ventricular beta-1/*immunology Receptor Adrenergic}, month = {Feb 9}, note = {Jahns, R Boivin, V Siegmund, C Inselmann, G Lohse, M J Boege, F Research Support, Non-U.S. Gov't United states Circulation Circulation. 1999 Feb 9;99(5):649-54.}, number = 5, pages = {649-54}, shorttitle = {Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure}, timestamp = {2010-12-14T18:22:40.000+0100}, title = {Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9950662}, volume = 99, year = 1999 }