Circulation, Vol 85, 1734-1742, Copyright © 1992 by American Heart Association
AL Caforio, M Grazzini, JM Mann, PJ Keeling, GF Bottazzo, WJ McKenna and S Schiaffino
BACKGROUND. Immunization with cardiac myosin induces experimental
autoimmune heart disease in genetically predisposed mice. These mice
produce heart-specific autoantibodies, some of which are directed against
the cardiac myosin isoform. METHODS AND RESULTS. We have reported the
presence of circulating heart-specific autoantibodies in 26% of patients
with idiopathic dilated cardiomyopathy (DCM) using indirect
immunofluorescence. To identify the autoantigen(s) recognized by
heart-specific autoantibodies in human disease, we tested, by Western
blotting, sera from 26 DCM patients, 14 of whom were cardiac
antibody-positive and 12 antibody-negative, as well as sera from 12
patients with cardiac failure from ischemic or valvular heart disease and
from 13 normal subjects who were cardiac antibody-negative. Crude
myofibrillar proteins and myosin preparations extracted from human atrial
or ventricular specimens were used as antigens. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis was performed. The proteins were
electrophoretically transferred to nitrocellulose sheets. The paper strips
were incubated in sera from patients or controls at 1:100 dilution; the
reaction was revealed with a peroxidase-labeled second antibody against
human immunoglobulin. Twelve of the 14 DCM sera (86%) containing
heart-specific antibodies reacted with both the alpha- (atrial specific)
and beta- (ventricular and slow skeletal) myosin heavy chain isoforms; none
of the 13 normal sera (p = 0.0001) and one of the 24 heart failure-negative
control sera (4%, p = 0.0001) contained antibodies against myosin heavy
chain. CONCLUSIONS. These findings indicate that alpha- and beta-cardiac
myosin heavy chain isoforms as in the murine model of autoimmune heart
disease are major autoantigens in patients with idiopathic DCM.
ARTICLES
Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy
Department of Cardiological Sciences, St. George's Hospital Medical School, London, England.
This article has been cited by other articles:
 |
|
 |
|
  M. W. Cunningham Turning Point in Myocarditis Circ. Res., August 28, 2009; 105(5): 403 - 405. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Kaya, S. Goser, S. J. Buss, F. Leuschner, R. Ottl, J. Li, M. Volkers, S. Zittrich, G. Pfitzer, N. R. Rose, et al. Identification of Cardiac Troponin I Sequence Motifs Leading to Heart Failure by Induction of Myocardial Inflammation and Fibrosis Circulation, November 11, 2008; 118(20): 2063 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L.P. Caforio, F. Calabrese, A. Angelini, F. Tona, A. Vinci, S. Bottaro, A. Ramondo, E. Carturan, S. Iliceto, G. Thiene, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis Eur. Heart J., June 1, 2007; 28(11): 1326 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Staudt, P. Eichler, C. Trimpert, S. B. Felix, and A. Greinacher Fc{gamma} Receptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1684 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L.P. Caforio, N. G. Mahon, M. K. Baig, F. Tona, R. T. Murphy, P. M. Elliott, and W. J. McKenna Prospective Familial Assessment in Dilated Cardiomyopathy: Cardiac Autoantibodies Predict Disease Development in Asymptomatic Relatives Circulation, January 2, 2007; 115(1): 76 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Fiaccavento, F. Carotenuto, M. Minieri, L. Masuelli, A. Vecchini, R. Bei, A. Modesti, L. Binaglia, A. Fusco, A. Bertoli, et al. {alpha}-Linolenic Acid-Enriched Diet Prevents Myocardial Damage and Expands Longevity in Cardiomyopathic Hamsters Am. J. Pathol., December 1, 2006; 169(6): 1913 - 1924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Warraich, E. Griffiths, A. Falconar, V. Pabbathi, C. Bell, G. Angelini, M.-S. Suleiman, and M. H. Yacoub Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship FASEB J, April 1, 2006; 20(6): 651 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A L. Caforio, L Daliento, A Angelini, S Bottaro, A Vinci, G Dequal, F Tona, S Iliceto, G Thiene, and W J McKenna Autoimmune myocarditis and dilated cardiomyopathy: focus on cardiac autoantibodies Lupus, September 1, 2005; 14(9): 652 - 655. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Tidholm and L. Jonsson Histologic Characterization of Canine Dilated Cardiomyopathy Vet. Pathol., January 1, 2005; 42(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. del Corsso, A. C. C. de Carvalho, H. F. Martino, and W. A. Varanda Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1928 - H1936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Staudt, Y. Staudt, M. Dorr, M. Bohm, F. Knebel, A. Hummel, L. Wunderle, M. Tiburcy, K. D. Wernecke, G. Baumann, et al. Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy J. Am. Coll. Cardiol., August 18, 2004; 44(4): 829 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Taylor, E. Havari, M. F. McInerney, R. Bronson, K. W. Wucherpfennig, and M. A. Lipes A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8 J. Immunol., February 15, 2004; 172(4): 2651 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W Mason Myocarditis and dilated cardiomyopathy: An inflammatory link Cardiovasc Res, October 15, 2003; 60(1): 5 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.B. Felix, A. Staudt, and G. Baumann Immunoadsorption as a new therapeutic principle for treatment of dilated cardiomyopathy Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I63 - I68. [Abstract] [PDF]
|
|
|
|
|
|
A. Staudt, M. Bohm, F. Knebel, Y. Grosse, C. Bischoff, A. Hummel, J. B. Dahm, A. Borges, N. Jochmann, K. D. Wernecke, et al. Potential Role of Autoantibodies Belonging to the Immunoglobulin G-3 Subclass in Cardiac Dysfunction Among Patients With Dilated Cardiomyopathy Circulation, November 5, 2002; 106(19): 2448 - 2453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Baba, T. Yoshikawa, and S. Ogawa Autoantibodies produced against sarcolemmal Na-K-ATPase: possible upstream targets of arrhythmias and sudden death in patients with dilated cardiomyopathy J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1153 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Burch Heart failure in the young Heart, August 1, 2002; 88(2): 198 - 202. [Full Text] [PDF]
|
|
|
|
 |
|
 A. L.P. Caforio, N. J. Mahon, F. Tona, and W. J. McKenna Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance Eur J Heart Fail, August 1, 2002; 4(4): 411 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Felix, A. Staudt, M. Landsberger, Y. Grosse, V. Stangl, T. Spielhagen, G. Wallukat, K. D. Wernecke, G. Baumann, and K. Stangl Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption J. Am. Coll. Cardiol., February 20, 2002; 39(4): 646 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Mann Autoimmunity, immunoglobulin adsorption and dilated cardiomyopathy: has the time come for randomized clinical trials? J. Am. Coll. Cardiol., July 1, 2001; 38(1): 184 - 186. [Full Text] [PDF]
|
|
|
|
|
|
A. Staudt, F. Schaper, V. Stangl, A. Plagemann, M. Bohm, K. Merkel, G. Wallukat, K. D. Wernecke, K. Stangl, G. Baumann, et al. Immunohistological Changes in Dilated Cardiomyopathy Induced by Immunoadsorption Therapy and Subsequent Immunoglobulin Substitution Circulation, June 5, 2001; 103(22): 2681 - 2686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L.P. Caforio, J. H. Goldman, M. K. Baig, N. J. Mahon, A. J. Haven, B. E. Souberbielle, D. W. Holt, A. G. Dalgleish, and W. J. McKenna Elevated serum levels of soluble interleukin-2 receptor, neopterin and {beta}-2-microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity and autoimmune pathogenesis Eur J Heart Fail, March 1, 2001; 3(2): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N G Mahon, A S Coonar, S Jeffery, F Coccolo, J Akiyu, B Zal, R Houlston, G E Levin, C Baboonian, W J McKenna, et al. Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy Heart, November 1, 2000; 84(5): 541 - 547. [Abstract] [Full Text]
|
|
|
|
|
|
S. B. Felix, A. Staudt, W. V. Dorffel, V. Stangl, K. Merkel, M. Pohl, W. D. Docke, S. Morgera, H. H. Neumayer, K. D. Wernecke, et al. Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: Three-month results from a randomized study J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1590 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Miyata, W. Minobe, M. R. Bristow, and L. A. Leinwand Myosin Heavy Chain Isoform Expression in the Failing and Nonfailing Human Heart Circ. Res., March 3, 2000; 86(4): 386 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Muller, G. Wallukat, M. Dandel, H. Bieda, K. Brandes, S. Spiegelsberger, E. Nissen, R. Kunze, and R. Hetzer Immunoglobulin Adsorption in Patients With Idiopathic Dilated Cardiomyopathy Circulation, February 1, 2000; 101(4): 385 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lauer, M. Schannwell, U. Kuhl, B.-E. Strauer, and H.-P. Schultheiss Antimyosin autoantibodies are associated with deterioration of systolic and diastolic left ventricular function in patients with chronic myocarditis J. Am. Coll. Cardiol., January 1, 2000; 35(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Kremastinos, P. Flevari, M. Spyropoulou, H. Vrettou, D. Tsiapras, and C. G. Stavropoulos-Giokas Association of Heart Failure in Homozygous {beta}-Thalassemia With the Major Histocompatibility Complex Circulation, November 16, 1999; 100(20): 2074 - 2078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bachmaier, N. Neu, R. S. M. Yeung, T. W. Mak, P. Liu, and J. M. Penninger Generation of Humanized Mice Susceptible to Peptide-Induced Inflammatory Heart Disease Circulation, April 13, 1999; 99(14): 1885 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S Dhalla, X. Liu, V. Panagia, and N. Takeda Subcellular remodeling and heart dysfunction in chronic diabetes Cardiovasc Res, November 1, 1998; 40(2): 239 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P F Currie, J H Goldman, A L P Caforio, A J Jacob, M K Baig, R P Brettle, A J Haven, N A Boon, and W J McKenna Cardiac autoimmunity in HIV related heart muscle disease Heart, June 1, 1998; 79(6): 599 - 604. [Abstract] [Full Text]
|
|
|
|
|
|
W. V. Dorffel, S. B. Felix, G. Wallukat, S. Brehme, K. Bestvater, T. Hofmann, F. X. Kleber, G. Baumann, and P. Reinke Short-term Hemodynamic Effects of Immunoadsorption in Dilated Cardiomyopathy Circulation, April 15, 1997; 95(8): 1994 - 1997. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. W. Dec and V. Fuster Idiopathic Dilated Cardiomyopathy N. Engl. J. Med., December 8, 1994; 331(23): 1564 - 1575. [Full Text]
|
|