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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1999 Oct;52(10):739–743. doi: 10.1136/jcp.52.10.739

Autoimmune markers are undetectable in end stage idiopathic dilated cardiomyopathy.

N de Leeuw 1, W J Melchers 1, D J Ruiter 1, A L Caforio 1, A H Balk 1, N de Jonge 1, J M Galama 1
PMCID: PMC501566  PMID: 10674030

Abstract

BACKGROUND: Autoreactive humoral and cellular immune responses may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Certain human leucocyte antigens (HLA) could also be linked to the development of IDC. AIM: To determine whether various markers of autoimmunity are present in the final phase of the disease, to substantiate the role of an autoimmune process in IDC. METHODS: 37 patients with end stage IDC were studied, together with 39 patients with end stage heart disease of known aetiology who were included for comparison. Multiple myocardial tissue samples from the explanted heart of each patient were evaluated (immuno)histologically. An indirect immunofluorescence assay was used to screen patient serum samples for the presence of heart specific autoantibodies. HLA class I and II frequencies were determined in each group and compared with HLA frequencies from healthy blood donors. RESULTS: Only scanty small mononuclear cell infiltrates were present in myocardial tissue of seven patients with IDC and of 11 patients with heart disease of known cause. The majority of these inflammatory cells were negative for T cell markers. All blood specimens were negative for heart specific autoantibodies and there was no apparent association of IDC with particular HLA phenotypes. CONCLUSIONS: These findings suggest that an active autoimmune process is not involved in the end stage of IDC.

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Selected References

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  1. Alarcon-Segovia D., Ruiz-Argüelles A., Llorente L. Broken dogma: penetration of autoantibodies into living cells. Immunol Today. 1996 Apr;17(4):163–164. doi: 10.1016/s0167-5699(96)90258-3. [DOI] [PubMed] [Google Scholar]
  2. Badorff C., Noutsias M., Kühl U., Schultheiss H. P. Cell-mediated cytotoxicity in hearts with dilated cardiomyopathy: correlation with interstitial fibrosis and foci of activated T lymphocytes. J Am Coll Cardiol. 1997 Feb;29(2):429–434. doi: 10.1016/s0735-1097(96)00475-5. [DOI] [PubMed] [Google Scholar]
  3. Caforio A. L., Bonifacio E., Stewart J. T., Neglia D., Parodi O., Bottazzo G. F., McKenna W. J. Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy. J Am Coll Cardiol. 1990 Jun;15(7):1527–1534. doi: 10.1016/0735-1097(90)92821-i. [DOI] [PubMed] [Google Scholar]
  4. Caforio A. L., Goldman J. H., Baig M. K., Haven A. J., Dalla Libera L., Keeling P. J., McKenna W. J. Cardiac autoantibodies in dilated cardiomyopathy become undetectable with disease progression. Heart. 1997 Jan;77(1):62–67. doi: 10.1136/hrt.77.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Caforio A. L., Grazzini M., Mann J. M., Keeling P. J., Bottazzo G. F., McKenna W. J., Schiaffino S. Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation. 1992 May;85(5):1734–1742. doi: 10.1161/01.cir.85.5.1734. [DOI] [PubMed] [Google Scholar]
  6. Caforio A. L., Keeling P. J., Zachara E., Mestroni L., Camerini F., Mann J. M., Bottazzo G. F., McKenna W. J. Evidence from family studies for autoimmunity in dilated cardiomyopathy. Lancet. 1994 Sep 17;344(8925):773–777. doi: 10.1016/s0140-6736(94)92339-6. [DOI] [PubMed] [Google Scholar]
  7. Caforio A. L., Martinetti M., Schwarz G., Bonifacio E., Gavazzi A., Graziano G., Lorini R., Cuccia M., McKenna W. J., Bottazzo G. F. Idiopathic dilated cardiomyopathy: lack of association between circulating organ-specific cardiac antibodies and HLA-DR antigens. Tissue Antigens. 1992 May;39(5):236–240. doi: 10.1111/j.1399-0039.1992.tb01941.x. [DOI] [PubMed] [Google Scholar]
  8. Carlquist J. F., Menlove R. L., Murray M. B., O'Connell J. B., Anderson J. L. HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies. Circulation. 1991 Feb;83(2):515–522. doi: 10.1161/01.cir.83.2.515. [DOI] [PubMed] [Google Scholar]
  9. Carlquist J. F., Ward R. H., Husebye D., Feolo M., Anderson J. L. Major histocompatibility complex class II gene frequencies by serologic and deoxyribonucleic acid genomic typing in idiopathic dilated cardiomyopathy. Am J Cardiol. 1994 Nov 1;74(9):918–920. doi: 10.1016/0002-9149(94)90586-x. [DOI] [PubMed] [Google Scholar]
  10. Cetta F., Michels V. V. The autoimmune basis of dilated cardiomyopathy. Ann Med. 1995 Apr;27(2):169–173. doi: 10.3109/07853899509031954. [DOI] [PubMed] [Google Scholar]
  11. Ferrari I., Levin M. J., Wallukat G., Elies R., Lebesgue D., Chiale P., Elizari M., Rosenbaum M., Hoebeke J. Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor. J Exp Med. 1995 Jul 1;182(1):59–65. doi: 10.1084/jem.182.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holzinger C., Schöllhammer A., Imhof M., Reinwald C., Kramer G., Zuckermann A., Wolner E., Steiner G. Phenotypic patterns of mononuclear cells in dilated cardiomyopathy. Circulation. 1995 Nov 15;92(10):2876–2885. doi: 10.1161/01.cir.92.10.2876. [DOI] [PubMed] [Google Scholar]
  13. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  14. Huber S. A. Autoimmunity in myocarditis: relevance of animal models. Clin Immunol Immunopathol. 1997 May;83(2):93–102. doi: 10.1006/clin.1997.4342. [DOI] [PubMed] [Google Scholar]
  15. Kasper E. K., Agema W. R., Hutchins G. M., Deckers J. W., Hare J. M., Baughman K. L. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol. 1994 Mar 1;23(3):586–590. doi: 10.1016/0735-1097(94)90740-4. [DOI] [PubMed] [Google Scholar]
  16. Latif N., Smith J., Dunn M. J., Yacoub M. H., Rose M. L. Complement-mediated cytotoxic activity of anti-heart antibodies present in the sera of patients with dilated cardiomyopathy. Autoimmunity. 1994;19(2):99–104. doi: 10.3109/08916939409009537. [DOI] [PubMed] [Google Scholar]
  17. Limas C. J. Cardiac autoantibodies in dilated cardiomyopathy: a pathogenetic role? Circulation. 1997 Apr 15;95(8):1979–1980. doi: 10.1161/01.cir.95.8.1979. [DOI] [PubMed] [Google Scholar]
  18. Magnusson Y., Wallukat G., Waagstein F., Hjalmarson A., Hoebeke J. Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect. Circulation. 1994 Jun;89(6):2760–2767. doi: 10.1161/01.cir.89.6.2760. [DOI] [PubMed] [Google Scholar]
  19. McKenna C. J., Codd M. B., McCann H. A., Sugrue D. D. Idiopathic dilated cardiomyopathy: familial prevalence and HLA distribution. Heart. 1997 Jun;77(6):549–552. doi: 10.1136/hrt.77.6.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mestroni L., Maisch B., McKenna W. J., Schwartz K., Charron P., Rocco C., Tesson F., Richter A., Wilke A., Komajda M. Guidelines for the study of familial dilated cardiomyopathies. Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy. Eur Heart J. 1999 Jan;20(2):93–102. doi: 10.1053/euhj.1998.1145. [DOI] [PubMed] [Google Scholar]
  21. Neumann D. A., Rose N. R., Ansari A. A., Herskowitz A. Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis. J Immunol. 1994 Jan 1;152(1):343–350. [PubMed] [Google Scholar]
  22. Pankuweit S., Portig I., Lottspeich F., Maisch B. Autoantibodies in sera of patients with myocarditis: characterization of the corresponding proteins by isoelectric focusing and N-terminal sequence analysis. J Mol Cell Cardiol. 1997 Jan;29(1):77–84. doi: 10.1006/jmcc.1996.0253. [DOI] [PubMed] [Google Scholar]
  23. Rose N. R., Neumann D. A., Herskowitz A. Autoimmune myocarditis: concepts and questions. Immunol Today. 1991 Aug;12(8):253–255. doi: 10.1016/0167-5699(91)90118-D. [DOI] [PubMed] [Google Scholar]
  24. Schipper R. F., Schreuder G. M., D'Amaro J., Oudshoorn M. HLA gene and haplotype frequencies in Dutch blood donors. Tissue Antigens. 1996 Nov;48(5):562–574. doi: 10.1111/j.1399-0039.1996.tb02670.x. [DOI] [PubMed] [Google Scholar]
  25. Thorsby E., Undlien D. The HLA associated predisposition to type 1 diabetes and other autoimmune diseases. J Pediatr Endocrinol Metab. 1996 Mar;9 (Suppl 1):75–88. doi: 10.1515/jpem.1996.9.s1.75. [DOI] [PubMed] [Google Scholar]
  26. Woodruff J. F. Viral myocarditis. A review. Am J Pathol. 1980 Nov;101(2):425–484. [PMC free article] [PubMed] [Google Scholar]

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