Skip to main content
SpringerLink
Log in

Effect of protein A immunoadsorption on T cell activation in patients with inflammatory dilated cardiomyopathy

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Immunoadsorption (IA) is used in patients with inflammatory dilative cardiomyopathy (iDCM) to remove cardiotoxic autoantibodies, and to improve myocardial function. Even if IA is used only once, the level of anti-cardiac antibodies remains low over time. Changes in cell-mediated immunity after IA may contribute to this observation. The aim of this study is to investigate the effect of IA on cell-mediated immunity especially on regulatory and early activated T cells.

Methods

Ten patients (50.1 ± 9.3 years) with chronic iDCM (with signs of myocardial inflammation in biopsies, but without persistence of virus genome), reduced left ventricular ejection fraction (EF < 35%) underwent IA. Blood samples were drawn before and after an IA course of 5 days, and 1, 3, and 6 months after IA. Leukocyte subpopulations were quantified by FACS analysis.

Results

Left ventricular systolic function improved on average at 6 months from 25.6 ± 4.9 to 37.3 ± 10.1% (p < 0.05). The left ventricular end-diastolic diameter was reduced after 6 months (63.3 ± 3.1 vs. 57.1 ± 4.1 mm; p < 0.05). IA therapy led to an increase of regulatory T cells (CD4+, CD25+ and CD127low) over time (up to 6 months). This was associated with a decrease of activated T cells (CD4+/CD69+ and CD8+/CD69+ cells) and CD28+ T cells (co-stimulatory cells), which was detectable for at least 6 months after IA.

Conclusion

It is suggested that changes in cell-mediated immunity contribute to the beneficial effect of IA on myocardial function, and on maintenance of reduced blood levels of cardiotoxic autoantibodies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Caforio AL, Mahon NJ, Tona F, McKenna WJ (2002) Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance. Eur J Heart Fail 4:411–417

    Article  PubMed  Google Scholar 

  2. Maisch B, Richter A, Sandmöller A, Portig I, Pankuweit S, BMBF-Heart Failure Network (2005) Inflammatory dilated cardiomyopathy (DCMI). Herz 30:535–544

    Article  PubMed  Google Scholar 

  3. Kallwellis-Opara A, Dörner A, Poller WC, Noutsias M, Kühl U, Schultheiss HP, Pauschinger M (2007) Autoimmunological features in inflammatory cardiomyopathy. Clin Res Cardiol 96:469–480

    Article  CAS  PubMed  Google Scholar 

  4. Staudt A, Böhm M, Knebel F, Grosse Y, Bischoff C, Hummel A, Dahm JB, Borges A, Jochmann N, Wernecke KD, Wallukat G, Baumann G, Felix SB (2002) Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy. Circulation 106:2448–2453

    Article  CAS  PubMed  Google Scholar 

  5. Wallukat G, Reinke P, Dörffel WV, Luther HP, Bestvater K, Felix SB, Baumann G (1996) Removal of autoantibodies in dilated cardiomyopathy by immunoadsorption. Int J Cardiol 54:191–195

    Article  CAS  PubMed  Google Scholar 

  6. Dörffel 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

    PubMed  Google Scholar 

  7. Felix SB, Staudt A, Dörffel WV, Stangl V, Merkel K, Pohl M, Döcke WD, Morgera S, Neumayer HH, Wernecke KD, Wallukat G, Stangl K, Baumann G (2000) Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: three-month results from a randomized study. J Am Coll Cardiol 35:1590–1598

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Staudt A, Schäper F, Stangl V, Plagemann A, Böhm M, Merkel K, Wallukat G, Wernecke KD, Stangl K, Baumann G, Felix SB (2001) Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution. Circulation 103:2681–2686

    CAS  PubMed  Google Scholar 

  10. Dörffel WV, Wallukat G, Dörffel Y, Felix SB, Baumann G (2004) Immunoadsorption in idiopathic dilated cardiomyopathy, a 3-year follow-up. Int J Cardiol 97:529–534

    Article  PubMed  Google Scholar 

  11. Staudt A, Hummel A, Ruppert J, Dörr M, Trimpert C, Birkenmeier K, Krieg T, Staudt Y, Felix SB (2006) Immunoadsorption in dilated cardiomyopathy: 6-month results from a randomised study. Am Heart J 152:712.e1–712.e6

    Article  Google Scholar 

  12. 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 

  13. 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(4):141–149

    PubMed  Google Scholar 

  14. Yoshikawa T, Baba A, Nagatomo Y (2009) Autoimmune mechanisms underlying dilated cardiomyopathy. Circ J 73:602–607

    Article  CAS  PubMed  Google Scholar 

  15. Lauer B, Schannwell M, Kühl U, Strauer BE, Schultheiss HP (2000) Antimyosin autoantibodies are associated with deterioration of systolic and diastolic left ventricular function in patients with chronic myocarditis. J Am Coll Cardiol 35:11–18

    Article  CAS  PubMed  Google Scholar 

  16. Cooper LT, Belohlavek M, Korinek J, Yoshifuku S, Sengupta PP, Burgstaler EA, Winters JL (2007) A pilot study to assess the use of protein A immunoadsorption for chronic dilated cardiomyopathy. J Clin Apher 22:210–214

    Article  PubMed  Google Scholar 

  17. Felix SB, Staudt A (2006) Non-specific immunoadsorption in patients with dilated cardiomyopathy: mechanisms and clinical effects. Int J Cardiol 112:30–33

    Article  PubMed  Google Scholar 

  18. Opavsky MA, Penninger J, Aitken K, Wen WH, Dawood F, Mak T, Liu P (1999) Susceptibility to myocarditis is dependent on the response of alpha–beta T lymphocytes to coxsackie viral infection. Circ Res 85:551–558

    CAS  PubMed  Google Scholar 

  19. Rönnblom LE, Forsberg H, Evrin PE (1991) Increased level of HLA-DR-expressing T lymphocytes in peripheral blood from patients with idiopathic dilated cardiomyopathy. Cardiology 78:161–167

    Article  PubMed  Google Scholar 

  20. Kuethe F, Braun RK, Foerster M, Schlenker Y, Sigusch HH, Kroegel C, Figulla HR (2006) Immunopathogenesis of dilated cardiomyopathy. Evidence for the role of TH2-type CD4+ T lymphocytes and association with myocardial HLA-DR expression. J Clin Immunol 26:33–39

    Article  CAS  PubMed  Google Scholar 

  21. Yndestad A, Holm AM, Müller F, Simonsen S, Froland SS, Gullestad L, Aukrust P (2003) Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure. Cardiovasc Res 60:141–146

    Article  CAS  PubMed  Google Scholar 

  22. Ueno A, Murasaki K, Hagiwara N, Kasanuki H (2007) Increases in circulating T lymphocytes expressing HLA-DR and CD40 ligand in patients with dilated cardiomyopathy. Heart Vessels 22:316–321

    Article  PubMed  Google Scholar 

  23. Huehnergarth KV, Mozaffarian D, Sullivan MD, Crabe BA, Wilkinson CW, Lwler RL, McDonald GB, Fishbein DP, Levy WC (2005) Usefulness of relative lymphocyte count as an independent predictor of death/urgent transplant in heart failure. Am J Cardiol 95:1492–1495

    Article  PubMed  Google Scholar 

  24. Kindermann I, Kindermann M, Kandolf R, Klingel K, Bültmann B, Müller T, Lindinger A, Böhm M (2008) Predictors of outcome in patients with suspected myocarditis. Circulation 118(6):639–648

    Article  PubMed  Google Scholar 

Download references

Conflict of interest statement

This work was supported by a research grant from Fresenius Medical Care, Bad Homburg, Germany.

Author information

Authors and Affiliations

  1. Herz- und Kreislaufzentrum der Ruhr-Universität, Standort St. Josef-Hospital, Gudrunstraße 56, 44791, Bochum, Germany

    Daniel Bulut, Tim Wichmann, Jan Börgel, Thomas Miebach & Andreas Mügge

  2. Herz- und Kreislaufzentrum der Ruhr-Universität, Standort BG Kliniken Bergmannsheil, Bürkle-de-la-Camp Platz 1, 44789, Bochum, Germany

    Michael Scheeler

  3. Division of Cardiology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany

    Daniel Bulut

Authors
  1. Daniel Bulut
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Scheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tim Wichmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan Börgel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Miebach
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andreas Mügge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Bulut.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bulut, D., Scheeler, M., Wichmann, T. et al. Effect of protein A immunoadsorption on T cell activation in patients with inflammatory dilated cardiomyopathy. Clin Res Cardiol 99, 633–638 (2010). https://doi.org/10.1007/s00392-010-0162-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-010-0162-6

Keywords

Search

Navigation