Correspondence
Specific Removal of β1-Adrenergic Autoantibodies from Patients with Idiopathic Dilated Cardiomyopathy
N Engl J Med 2002; 347:1806November 28, 2002
- Article
To the Editor:
The pathophysiologic relevance of autoantibodies against cardiac proteins in the induction or maintenance of idiopathic dilated cardiomyopathy is still unclear. It has been shown that induction of antibodies against cardiac β1-adrenergic–receptor structures in rabbits leads to significant cardiac dilatation.1,2 Examinations of cardiac myocytes from neonatal rats have shown that this antibody type isolated from patients with idiopathic dilated cardiomyopathy acts like a β-adrenergic agonist.3 Removal of class G immunoglobulins from plasma has been shown to improve cardiac performance within one year after immunoadsorption in patients with idiopathic dilated cardiomyopathy.4 Since immunoadsorption removes a whole class of immunoglobulins, all autoantibodies of that particular class were eliminated. We report the effect on cardiac performance of selective elimination of autoantibodies against the β1-adrenergic receptor after one year in eight patients. The prevalence of these autoantibodies in patients with idiopathic dilated cardiomyopathy is about 80 percent.4
Specific immunoadsorption was performed with peptide columns (Coraffin, Affina). The peptides mimic the autoantibody-binding epitopes of the β1-adrenergic receptor. All eight patients (one woman and seven men; mean [±SE] age, 49.4±9.4 years; mean duration of heart failure, 7.7±7.0 years) had idiopathic dilated cardiomyopathy: on base-line echocardiography, the two-dimensional left ventricular ejection fraction was 28.5±6.1 percent; the left ventricular diastolic dimension, 69.3±8.5 mm; and the maximal wall-motion velocity in systole, 4.9±0.6 cm per second. All the patients had been receiving full, standard medication for heart failure for at least six months, including beta-blockers, angiotensin-converting–enzyme inhibitors, and aldosterone antagonists. Autoantibody removal was performed on five consecutive days, with a reduction from 5.0±0.5 laboratory units (LU) at base line to 1.2±0.6 LU after five days. After one year, the ejection fraction had increased to 36.6.±10.7 percent (95 percent confidence interval of the P value, 0.002 to 0.02 by the Wilcoxon test with bootstrapping simulation); the left ventricular dimension had become 65.6±14.2 mm (P value, 0.10 to 0.12 for the comparison with base line), and maximal wall velocity had increased to 7.2±2.2 cm per second (P value, 0.006 to 0.01 for the comparison with base line). The autoantibody level remained at 0.6±0.6 LU (P value, 0.001 to 0.004) one year after elimination.
Until recently, no column was available to remove selectively the specific type of autoantibody against the β1-adrenergic receptor that was hypothesized to influence cardiac performance negatively. Substitution of immunoglobulins, a widely used procedure after unselective immunoadsorption, can be avoided. Selective removal of autoantibodies against β1-adrenergic receptors had favorable effects on cardiac performance in patients with idiopathic dilated cardiomyopathy.
4 ReferencesGerd Wallukat, Ph.D.
Max Delbrück Center for Molecular Medicine, 13125 Berlin, GermanyJohannes Müller, M.D.
Roland Hetzer, M.D., Ph.D.
Deutsches Herzzentrum Berlin, 13353 Berlin, Germany
jmueller@dhzb.de 1
Matsui S ,Fu ML ,Katsuda S , et al. Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol 1997;29:641-655
CrossRef | Web of Science | Medline2
Iwata M ,Yoshikawa T ,Baba A , et al. Autoimmunity against the second extracellular loop of beta(1)-adrenergic receptors induces beta-adrenergic receptor desensitization and myocardial hypertrophy in vivo. Circ Res 2001;88:578-586
Web of Science | Medline3
Magnusson Y ,Wallukat G ,Waagstein F ,Hjalmarson A ,Hoebeke J . Autoimmunity in idiopathic dilated cardiomyopathy: characterization of antibodies against the beta 1-adrenoreceptor with positive chronotropic effect. Circulation 1994;89:2760-2767
Web of Science | Medline4
Muller J ,Wallukat G ,Dandel M , et el. Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy. Circulation 2000;101:385-391
Web of Science | Medline
- Citing Articles (25)
Citing Articles
1
Yusuke Sugi, Hideo Yasukawa, Hisashi Kai, Daisuke Fukui, Nobuyoshi Futamata, Kazuhisa Mawatari, Toyoharu Oba, Nobutaka Nagata, Sachiko Kyougoku, Mitsuhisa Koga, Tsutomu Imaizumi. (2011) Reduction and activation of circulating dendritic cells in patients with decompensated heart failure. International Journal of Cardiology 147:2, 258-264
CrossRef2
Udi Nussinovitch, Yehuda Shoenfeld. (2011) The Diagnostic and Clinical Significance of Anti-Muscarinic Receptor Autoantibodies. Clinical Reviews in Allergy & Immunology
CrossRef3
Udi Nussinovitch, Yehuda Shoenfeld. (2011) The Clinical and Diagnostic Significance of Anti-myosin Autoantibodies in Cardiac Disease. Clinical Reviews in Allergy & Immunology
CrossRef4
Yuji Nagatomo, Akiyasu Baba, Hiroyuki Ito, Kotaro Naito, Akihiro Yoshizawa, Yasuo Kurita, Iwao Nakamura, Toshiaki Monkawa, Takashi Matsubara, Yasuhisa Wakabayashi, Satoshi Ogawa, Makoto Akaishi, Tsutomu Yoshikawa. (2011) Specific immunoadsorption therapy using a tryptophan column in patients with refractory heart failure due to dilated cardiomyopathy. Journal of Clinical Apheresis 26:1, 1-8
CrossRef5
J. Ren, H.-L. Wei, L. Xu, L.-Y. Jia. 2011. Blood Detoxication. , 729-739.
CrossRef6
Udi Nussinovitch, Yehuda Shoenfeld. (2010) The Clinical Significance of Anti-Beta-1 Adrenergic Receptor Autoantibodies in Cardiac Disease. Clinical Reviews in Allergy & Immunology
CrossRef7
Enno Schmidt, Detlef Zillikens. (2010) Immunoadsorption in dermatology. Archives of Dermatological Research 302:4, 241-253
CrossRef8
Charline Wehlou, Joris R Delanghe. (2009) Detection of antibodies in cardiac autoimmunity. Clinica Chimica Acta 408:1-2, 114-122
CrossRef9
Yuji Nagatomo, Tsutomu Yoshikawa, Takashi Kohno, Akihiro Yoshizawa, Akiyasu Baba, Toshihisa Anzai, Tomomi Meguro, Toru Satoh, Satoshi Ogawa. (2009) A Pilot Study on the Role of Autoantibody Targeting the β1-Adrenergic Receptor in the Response to β-blocker Therapy for Congestive Heart Failure. Journal of Cardiac Failure 15:3, 224-232
CrossRef10
Jason M. Lappé, Clara M. Pelfrey, W.H. Wilson Tang. (2008) Recent Insights Into the Role of Autoimmunity in Idiopathic Dilated Cardiomyopathy. Journal of Cardiac Failure 14:6, 521-530
CrossRef11
Jiahao Liu, Weike Mao, Chikao Iwai, Shuji Fukuoka, Raju Vulapalli, Huanlei Huang, Tingchung Wang, Virendra K. Sharma, Shey-Shing Sheu, Michael Fu, Chang-seng Liang. (2008) Adoptive passive transfer of rabbit β1-adrenoceptor peptide immune cardiomyopathy into the Rag2−/− mouse: Participation of the ER stress. Journal of Molecular and Cellular Cardiology 44:2, 304-314
CrossRef12
Edwin A. Burgstaler, Leslie T. Cooper, Jeffrey L. Winters. (2007) Treatment of chronic dilated cardiomyopathy with immunoadsorption using the staphylococcal A-Agarose column: A comparison of immunoglobulin reduction using two different techniques. Journal of Clinical Apheresis 22:4, 224-232
CrossRef13
Leslie T. Cooper, Marek Belohlavek, Josef Korinek, Shiro Yoshifuku, Partho P. Sengupta, Edwin A. Burgstaler, Jeffrey L. Winters. (2007) A pilot study to assess the use of protein a immunoadsorption for chronic dilated cardiomyopathy. Journal of Clinical Apheresis 22:4, 210-214
CrossRef14
Viacheslav O. Nikolaev, Valérie Boivin, Stefan Störk, Christiane E. Angermann, Georg Ertl, Martin J. Lohse, Roland Jahns. (2007) A Novel Fluorescence Method for the Rapid Detection of Functional β1-Adrenergic Receptor Autoantibodies in Heart Failure. Journal of the American College of Cardiology 50:5, 423-431
CrossRef15
V. Labovsky, C. R. Smulski, K. Gómez, G. Levy, M. J. Levin. (2007) Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease. Clinical & Experimental Immunology 148:3, 440-449
CrossRef16
Josep E. Herrero-González, Olaf Brauns, Ralf Egner, Wolfgang Rönspeck, José M. Mascaró, Marcel F. Jonkman, Detlef Zillikens, Cassian Sitaru. (2006) Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation inducedin vitroby autoantibodies from pemphigoid gestationis patients. European Journal of Immunology 36:4, 1039-1048
CrossRef17
Reza Mobini, Bert Andersson. (2005) The therapeutic potential of immune therapy in idiopathic dilated cardiomyopathy. Future Cardiology 1:5, 675-682
CrossRef18
Torsten Christ, Esther Adolph, Stefan Schindelhauer, Erich Wettwer, Dobromir Dobrev, Gerd Wallukat, Ursula Ravens. (2005) Effects of Immunoglobulin G from Patients with Dilated Cardiomyopathy on Rat Cardiomyocytes. Basic <html_ent glyph="@amp;" ascii="&"/> Clinical Pharmacology <html_ent glyph="@amp;" ascii="&"/> Toxicology 96:6, 445-452
CrossRef19
ALON Y. HERSHKO, YAAKOV NAPARSTEK. (2005) Removal of Pathogenic Autoantibodies by Immunoadsorption. Annals of the New York Academy of Sciences 1051:1, 635-646
CrossRef20
Ralf Dechend, Dominik N. Müller, Gerd Wallukat, Volker Homuth, Manja Krause, Joachim Dudenhausen, Friedrich C. Luft. (2005) Activating auto-antibodies against the AT1 receptor in preeclampsia. Autoimmunity Reviews 4:1, 61-65
CrossRef21
Ralf Dechend, Dominik N. Müller, Gerd Wallukat, Volker Homuth, Manya Krause, Joachim Dudenhausen, Friedrich C. Luft. (2004) AT1 receptor agonistic antibodies, hypertension, and preeclampsia. Seminars in Nephrology 24:6, 571-579
CrossRef22
Reza Mobini, Hans Maschke, Finn Waagstein. (2004) New insights into the pathogenesis of dilated cardiomyopathy: possible underlying autoimmune mechanisms and therapy. Autoimmunity Reviews 3:4, 277-284
CrossRef23
E. MAHLER, J. HOEBEKE, M. J. LEVIN. (2004) Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2beta protein in patients with chronic Chagas' heart disease. Clinical and Experimental Immunology 136:3, 527-534
CrossRef24
Roland Jahns, Valérie Boivin, Lutz Hein, Sven Triebel, Christiane E. Angermann, Georg Ertl, Martin J. Lohse. (2004) Direct evidence for a β1-adrenergic receptor–directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. Journal of Clinical Investigation 113:10, 1419-1429
CrossRef25
Wolfgang Ronspeck, Roland Brinckmann, Ralf Egner, Frank Gebauer, Dirk Winkler, Petra Jekow, Gerd Wallukat, Johannes Muller, Rudolf Kunze. (2003) Peptide Based Adsorbers for Therapeutic Immunoadsorption. Therapeutic Apheresis and Dialysis 7:1, 91-97
CrossRef
