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Impact of troponin I-autoantibodies in chronic dilated and ischemic cardiomyopathy

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Abstract

The aim of this study was to investigate the prognostic value of circulating troponin I (TNI)-autoantibodies in plasma of patients with chronic heart failure. Sera of 390 heart failure patients were tested for the presence of anti-TNI antibodies by enzyme-linked immunosorbent assay (ELISA), including 249 (63.8% of total) patients with dilated cardiomyopathy (DCM) and 141 (36.2% of total) patients with ischemic cardiomyopathy (ICM). A total of 72 patients (18.5% of total) were female and 318 (81.5% of total) were male. Mean patient age was 54.6 ± 11.3 years and mean follow-up time was 3.8 ± 3.2 years. TNI-autoantibodies (titer of ≥1:40) were detected in 73 out of 390 patients (18.7% of total). In TNI-autoantibody positive patients mean left ventricular ejection fraction (LVEF) was 27.6 ± 5.8%, compared to 25.8 ± 5.9% in TNI-autoantibody negative patients, P = 0.03. The combined end-point of death (n = 118, 30.3% of total) or heart transplantation (HTX) (n = 44, 11.3% of total) was reached in 162 patients (41.5% of total). Kaplan–Meier analysis demonstrated superior survival (combined end-point of death or HTX) in patients with DCM versus ICM (P = 0.0198) and TNI-autoantibody positive patients versus TNI-autoantibody negative patients (P = 0.0348). Further subgroup analysis revealed a favorable outcome in TNI-positive patients with heart failure if the patients suffered from DCM (P = 0.0334), whereas TNI-autoantibody status in patients with ICM was not associated with survival (P = 0.8486). In subsequent multivariate Weibull-analysis, a positive TNI serostatus was associated with a significantly lower all-cause mortality in DCM patients (P = 0.0492). The presence of TNI-autoantibodies in plasma is associated with an improved survival in patients with chronic DCM, but not ICM. This might possibly indicate a prophylactic effect of TNI-autoantibodies in this subgroup of patients, encouraging further studies into possible protective effects of antibodies against certain cardiac target structures.

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Abbreviations

BSA:

Bovine serum albumin

DCM:

Dilated cardiomyopathy

ELISA:

Enzyme-linked immunosorbent assay

IA:

Extracorporeal immunoadsorption

HTX:

Heart transplantation

HRP:

Horseradish peroxidase

h:

Hour

Ig:

Immunoglobulin

ICM:

Ischemic cardiomyopathy

LVEF:

Left ventricular ejection fraction

NYHA:

New York Heart Association functional class

PBS:

Phosphate buffered saline

RT:

Room temperature

TNI:

Troponin I

References

  1. Caforio AL, Vinci A, Iliceto S (2008) Anti-heart autoantibodies in familial dilated cardiomyopathy. Autoimmunity 41:462–469

    Article  CAS  PubMed  Google Scholar 

  2. Deubner N, Berliner D, Schlipp A, Gelbrich G, Caforio AL, Felix SB, Fu M, Katus H, Angermann CE, Lohse MJ, Ertl G, Stork S, Jahns R (2010) Cardiac beta1-adrenoceptor autoantibodies in human heart disease: rationale and design of the Etiology, Titre-Course, and Survival (ETiCS) Study. Eur J Heart Fail 12:753–762

    Article  CAS  PubMed  Google Scholar 

  3. Doesch AO, Konstandin M, Celik S, Kristen A, Frankenstein L, Hardt S, Goeser S, Kaya Z, Katus HA, Dengler TJ (2009) Effects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy. J Clin Apher 24:141–149

    PubMed  Google Scholar 

  4. Dorffel WV, Felix SB, Wallukat G, Brehme S, Bestvater K, Hofmann T, Kleber FX, Baumann G, Reinke P (1997) Short-term hemodynamic effects of immunoadsorption in dilated cardiomyopathy. Circulation 95:1994–1997

    CAS  PubMed  Google Scholar 

  5. Felix SB, Staudt A, Landsberger M, Grosse Y, Stangl V, Spielhagen T, Wallukat G, Wernecke KD, Baumann G, Stangl K (2002) Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption. J Am Coll Cardiol 39:646–652

    Article  CAS  PubMed  Google Scholar 

  6. Goser S, Andrassy M, Buss SJ, Leuschner F, Volz CH, Ottl R, Zittrich S, Blaudeck N, Hardt SE, Pfitzer G, Rose NR, Katus HA, Kaya Z (2006) Cardiac troponin I but not cardiac troponin T induces severe autoimmune inflammation in the myocardium. Circulation 114:1693–1702

    Article  PubMed  Google Scholar 

  7. Jahns R, Boivin V, Hein L, Triebel S, Angermann CE, Ertl G, Lohse MJ (2004) Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. J Clin Invest 113:1419–1429

    CAS  PubMed  Google Scholar 

  8. Jahns R, Boivin V, Schwarzbach V, Ertl G, Lohse MJ (2008) Pathological autoantibodies in cardiomyopathy. Autoimmunity 41:454–461

    Article  CAS  PubMed  Google Scholar 

  9. Jahns R, Boivin V, Siegmund C, Inselmann G, Lohse MJ, Boege F (1999) Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure. Circulation 99:649–654

    CAS  PubMed  Google Scholar 

  10. Kaya Z, Katus HA (2010) Role of autoimmunity in dilated cardiomyopathy. Basic Res Cardiol 105:7–8

    Article  PubMed  Google Scholar 

  11. Lazzerini PE, Capecchi PL, Guideri F, Acampa M, Selvi E, Bisogno S, Galeazzi M, Laghi-Pasini F (2008) Autoantibody-mediated cardiac arrhythmias: mechanisms and clinical implications. Basic Res Cardiol 103:1–11

    Article  CAS  PubMed  Google Scholar 

  12. Leuschner F, Li J, Goser S, Reinhardt L, Ottl R, Bride P, Zehelein J, Pfitzer G, Remppis A, Giannitsis E, Katus HA, Kaya Z (2008) Absence of auto-antibodies against cardiac troponin I predicts improvement of left ventricular function after acute myocardial infarction. Eur Heart J 29:1949–1955

    Article  PubMed  Google Scholar 

  13. Macabasco-O’Connell A, Crawford MH, Stotts N, Stewart A, Froelicher ES (2010) Gender and racial differences in psychosocial factors of low-income patients with heart failure. Heart Lung 39:2–11

    Article  PubMed  Google Scholar 

  14. Magnusson Y, Wallukat G, Waagstein F, Hjalmarson A, Hoebeke J (1994) Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect. Circulation 89:2760–2767

    CAS  PubMed  Google Scholar 

  15. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113:1807–1816

    Article  PubMed  Google Scholar 

  16. Mobini R, Staudt A, Felix SB, Baumann G, Wallukat G, Deinum J, Svensson H, Hjalmarson A, Fu M (2003) Hemodynamic improvement and removal of autoantibodies against beta1-adrenergic receptor by immunoadsorption therapy in dilated cardiomyopathy. J Autoimmun 20:345–350

    Article  CAS  PubMed  Google Scholar 

  17. Nikolaev VO, Boivin V, Stork S, Angermann CE, Ertl G, Lohse MJ, Jahns R (2007) A novel fluorescence method for the rapid detection of functional beta1-adrenergic receptor autoantibodies in heart failure. J Am Coll Cardiol 50:423–431

    Article  CAS  PubMed  Google Scholar 

  18. Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N, Honjo T (2003) Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med 9:1477–1483

    Article  CAS  PubMed  Google Scholar 

  19. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 93:841–842

    CAS  PubMed  Google Scholar 

  20. Robbins SL, Kumar V, Cotran RS (2003) Robbins basic pathology. Saunders, Philadelphia

    Google Scholar 

  21. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik AJ (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367

    CAS  PubMed  Google Scholar 

  22. Staudt A, Dorr M, Staudt Y, Bohm M, Probst M, Empen K, Plotz S, Maschke HE, Hummel A, Baumann G, Felix SB (2005) Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption. Am Heart J 150:729–736

    Article  CAS  PubMed  Google Scholar 

  23. Staudt A, Eichler P, Trimpert C, Felix SB, Greinacher A (2007) Fc(gamma) receptors IIa on cardiomyocytes and their potential functional relevance in dilated cardiomyopathy. J Am Coll Cardiol 49:1684–1692

    Article  CAS  PubMed  Google Scholar 

  24. Stork S, Boivin V, Horf R, Hein L, Lohse MJ, Angermann CE, Jahns R (2006) Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy. Am Heart J 152:697–704

    Article  PubMed  Google Scholar 

  25. Voigt A, Bartel K, Egerer K, Trimpert C, Feist E, Gericke C, Kandolf R, Klingel K, Kuckelkorn U, Stangl K, Felix SB, Baumann G, Kloetzel PM, Staudt A (2010) Humoral anti-proteasomal autoimmunity in dilated cardiomyopathy. Basic Res Cardiol 105:9–18

    Article  CAS  PubMed  Google Scholar 

  26. Voigt A, Trimpert C, Bartel K, Egerer K, Kuckelkorn U, Feist E, Gericke C, Klingel K, Kandolf R, Felix SB, Baumann G, Kloetzel PM, Stangl K, Staudt A (2010) Lack of evidence for a pathogenic role of proteasome-directed autoimmunity in dilated cardiomyopathy. Basic Res Cardiol 105:557–567

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a research grant from Fresenius Medical Care, Bad Homburg v.d.H., Germany, to Andreas O. Doesch, all other authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Cardiology, University of Heidelberg, 69120, Heidelberg, Germany

    Andreas O. Doesch, Susanne Mueller, Manfred Nelles, Mathias Konstandin, Sultan Celik, Lutz Frankenstein, Stefan Goeser, Ziya Kaya, Christian Zugck & Hugo A. Katus

  2. Department of Cardiac Surgery, University of Heidelberg, 69120, Heidelberg, Germany

    Achim Koch

  3. Medizinische Klinik III, Kardiologie, Angiologie, Pulmologie, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Andreas O. Doesch

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  1. Andreas O. Doesch
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  2. Susanne Mueller
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  3. Manfred Nelles
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  5. Sultan Celik
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  11. Hugo A. Katus
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Correspondence to Andreas O. Doesch.

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Doesch, A.O., Mueller, S., Nelles, M. et al. Impact of troponin I-autoantibodies in chronic dilated and ischemic cardiomyopathy. Basic Res Cardiol 106, 25–35 (2011). https://doi.org/10.1007/s00395-010-0126-z

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  • DOI: https://doi.org/10.1007/s00395-010-0126-z

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