A novel fluorescence method for the rapid detection of functional
beta1-adrenergic receptor autoantibodies in heart failure
V. Nikolaev, V. Boivin, S. Stork, C. Angermann, G. Ertl, M. Lohse, and R. Jahns. J Am Coll Cardiol, 50 (5):
423-31(July 2007)Nikolaev, Viacheslav O Boivin, Valerie Stork, Stefan Angermann, Christiane
E Ertl, Georg Lohse, Martin J Jahns, Roland Comparative Study Research
Support, Non-U.S. Gov't United States Journal of the American College
of Cardiology J Am Coll Cardiol. 2007 Jul 31;50(5):423-31. Epub 2007
Jul 13..
Abstract
OBJECTIVES: This study sought to develop a rapid method for the detection
of activating autoantibodies directed against the beta1-adrenoceptor
(anti-beta1-Abs) in patients with heart failure. BACKGROUND: The
anti-beta1-Abs are supposed to play a pathophysiological role in
heart failure. However, there is no reliable method for their detection.
With a complex screening strategy (enzyme-linked immunosorbent assay,
immunofluorescence, cyclic adenosine monophosphate cAMP-radioimmunoassay)
we have previously identified antibodies targeting the second extracellular
beta1-receptor loop (anti-beta1-EC(II)) in 13% of patients with ischemic
cardiomyopathy (ICM) and in 26% with dilated cardiomyopathy (DCM).
METHODS: To detect anti-beta1-Abs, we measured beta1-receptor-mediated
increases in intracellular cAMP by fluorescence resonance energy
transfer using a highly sensitive cAMP sensor (Epac1-based fluorescent
cAMP sensor). RESULTS: The immunoglobulin G (IgG) prepared from 77
previously antibody-typed patients (22 ICM/55 DCM) and 50 matched
control patients was analyzed. The IgG from all 22 previously anti-beta1-EC(II)-positive
patients (5 ICM/17 DCM) induced a marked cAMP increase, indicating
receptor activation (49.8 +/- 4.2% of maximal isoproterenol-induced
signal). The IgG from control patients and 32 previously anti-beta1-EC(II)-negative
patients (17 ICM/15 DCM) did not significantly affect cAMP. Surprisingly,
our technology detected anti-beta1-Abs in 23 DCM patients formerly
judged antibody-negative, but their cAMP signals were generally lower
(31.3 +/- 6.8%) than in the previous group. "Low"-activator anti-beta1-Abs
were blocked preferentially by peptides corresponding to the first,
and "high"-activator anti-beta1-Abs by peptides corresponding to
the second beta1-extracellular loop. Beta-blockers alone failed to
fully prevent anti-beta1-EC(II)-induced receptor activation, which
could be achieved, however, by the addition of beta1-EC(II) peptides.
CONCLUSIONS: Our novel method of detecting anti-beta1-Abs proved
to be fast and highly sensitive. It also revealed an insufficient
ability of beta-blockers to prevent anti-beta1-EC(II)-induced receptor
activation, which opens new venues for the research on anti-beta1-Abs
and eventual treatment options in heart failure.
Nikolaev, Viacheslav O Boivin, Valerie Stork, Stefan Angermann, Christiane
E Ertl, Georg Lohse, Martin J Jahns, Roland Comparative Study Research
Support, Non-U.S. Gov't United States Journal of the American College
of Cardiology J Am Coll Cardiol. 2007 Jul 31;50(5):423-31. Epub 2007
Jul 13.
%0 Journal Article
%1 Nikolaev2007a
%A Nikolaev, V. O.
%A Boivin, V.
%A Stork, S.
%A Angermann, C. E.
%A Ertl, G.
%A Lohse, M. J.
%A Jahns, R.
%D 2007
%J J Am Coll Cardiol
%K & Adrenergic Aged Autoantibodies/*analysis/drug Biological Energy Epitopes Failure/drug Female Fluorescence Heart Humans Male Markers/analysis Middle Reference Resonance Sensitivity Specificity Transfer/instrumentation/*methods Values and beta-1/antagonists beta-Antagonists/therapeutic effects inhibitors/*immunology therapy/*immunology use Receptor
%N 5
%P 423-31
%T A novel fluorescence method for the rapid detection of functional
beta1-adrenergic receptor autoantibodies in heart failure
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17662395
%V 50
%X OBJECTIVES: This study sought to develop a rapid method for the detection
of activating autoantibodies directed against the beta1-adrenoceptor
(anti-beta1-Abs) in patients with heart failure. BACKGROUND: The
anti-beta1-Abs are supposed to play a pathophysiological role in
heart failure. However, there is no reliable method for their detection.
With a complex screening strategy (enzyme-linked immunosorbent assay,
immunofluorescence, cyclic adenosine monophosphate cAMP-radioimmunoassay)
we have previously identified antibodies targeting the second extracellular
beta1-receptor loop (anti-beta1-EC(II)) in 13% of patients with ischemic
cardiomyopathy (ICM) and in 26% with dilated cardiomyopathy (DCM).
METHODS: To detect anti-beta1-Abs, we measured beta1-receptor-mediated
increases in intracellular cAMP by fluorescence resonance energy
transfer using a highly sensitive cAMP sensor (Epac1-based fluorescent
cAMP sensor). RESULTS: The immunoglobulin G (IgG) prepared from 77
previously antibody-typed patients (22 ICM/55 DCM) and 50 matched
control patients was analyzed. The IgG from all 22 previously anti-beta1-EC(II)-positive
patients (5 ICM/17 DCM) induced a marked cAMP increase, indicating
receptor activation (49.8 +/- 4.2% of maximal isoproterenol-induced
signal). The IgG from control patients and 32 previously anti-beta1-EC(II)-negative
patients (17 ICM/15 DCM) did not significantly affect cAMP. Surprisingly,
our technology detected anti-beta1-Abs in 23 DCM patients formerly
judged antibody-negative, but their cAMP signals were generally lower
(31.3 +/- 6.8%) than in the previous group. "Low"-activator anti-beta1-Abs
were blocked preferentially by peptides corresponding to the first,
and "high"-activator anti-beta1-Abs by peptides corresponding to
the second beta1-extracellular loop. Beta-blockers alone failed to
fully prevent anti-beta1-EC(II)-induced receptor activation, which
could be achieved, however, by the addition of beta1-EC(II) peptides.
CONCLUSIONS: Our novel method of detecting anti-beta1-Abs proved
to be fast and highly sensitive. It also revealed an insufficient
ability of beta-blockers to prevent anti-beta1-EC(II)-induced receptor
activation, which opens new venues for the research on anti-beta1-Abs
and eventual treatment options in heart failure.
@article{Nikolaev2007a,
abstract = {OBJECTIVES: This study sought to develop a rapid method for the detection
of activating autoantibodies directed against the beta1-adrenoceptor
(anti-beta1-Abs) in patients with heart failure. BACKGROUND: The
anti-beta1-Abs are supposed to play a pathophysiological role in
heart failure. However, there is no reliable method for their detection.
With a complex screening strategy (enzyme-linked immunosorbent assay,
immunofluorescence, cyclic adenosine monophosphate [cAMP]-radioimmunoassay)
we have previously identified antibodies targeting the second extracellular
beta1-receptor loop (anti-beta1-EC(II)) in 13% of patients with ischemic
cardiomyopathy (ICM) and in 26% with dilated cardiomyopathy (DCM).
METHODS: To detect anti-beta1-Abs, we measured beta1-receptor-mediated
increases in intracellular cAMP by fluorescence resonance energy
transfer using a highly sensitive cAMP sensor (Epac1-based fluorescent
cAMP sensor). RESULTS: The immunoglobulin G (IgG) prepared from 77
previously antibody-typed patients (22 ICM/55 DCM) and 50 matched
control patients was analyzed. The IgG from all 22 previously anti-beta1-EC(II)-positive
patients (5 ICM/17 DCM) induced a marked cAMP increase, indicating
receptor activation (49.8 +/- 4.2% of maximal isoproterenol-induced
signal). The IgG from control patients and 32 previously anti-beta1-EC(II)-negative
patients (17 ICM/15 DCM) did not significantly affect cAMP. Surprisingly,
our technology detected anti-beta1-Abs in 23 DCM patients formerly
judged antibody-negative, but their cAMP signals were generally lower
(31.3 +/- 6.8%) than in the previous group. "Low"-activator anti-beta1-Abs
were blocked preferentially by peptides corresponding to the first,
and "high"-activator anti-beta1-Abs by peptides corresponding to
the second beta1-extracellular loop. Beta-blockers alone failed to
fully prevent anti-beta1-EC(II)-induced receptor activation, which
could be achieved, however, by the addition of beta1-EC(II) peptides.
CONCLUSIONS: Our novel method of detecting anti-beta1-Abs proved
to be fast and highly sensitive. It also revealed an insufficient
ability of beta-blockers to prevent anti-beta1-EC(II)-induced receptor
activation, which opens new venues for the research on anti-beta1-Abs
and eventual treatment options in heart failure.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Nikolaev, V. O. and Boivin, V. and Stork, S. and Angermann, C. E. and Ertl, G. and Lohse, M. J. and Jahns, R.},
biburl = {https://www.bibsonomy.org/bibtex/2e8ec9843465f59be295c932409d6d40b/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {ef9d1f15562a5fef80622c8bff68928b},
intrahash = {e8ec9843465f59be295c932409d6d40b},
issn = {1558-3597 (Electronic) 1558-3597 (Linking)},
journal = {J Am Coll Cardiol},
keywords = {& Adrenergic Aged Autoantibodies/*analysis/drug Biological Energy Epitopes Failure/drug Female Fluorescence Heart Humans Male Markers/analysis Middle Reference Resonance Sensitivity Specificity Transfer/instrumentation/*methods Values and beta-1/antagonists beta-Antagonists/therapeutic effects inhibitors/*immunology therapy/*immunology use Receptor},
month = {Jul 31},
note = {Nikolaev, Viacheslav O Boivin, Valerie Stork, Stefan Angermann, Christiane
E Ertl, Georg Lohse, Martin J Jahns, Roland Comparative Study Research
Support, Non-U.S. Gov't United States Journal of the American College
of Cardiology J Am Coll Cardiol. 2007 Jul 31;50(5):423-31. Epub 2007
Jul 13.},
number = 5,
pages = {423-31},
shorttitle = {A novel fluorescence method for the rapid detection of functional
beta1-adrenergic receptor autoantibodies in heart failure},
timestamp = {2010-12-14T18:22:41.000+0100},
title = {A novel fluorescence method for the rapid detection of functional
beta1-adrenergic receptor autoantibodies in heart failure},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17662395},
volume = 50,
year = 2007
}