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Cellular immune mechanisms in myocarditis

Zelluläre Immunmechanismen bei Myokarditis

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Abstract

The introduction of immunohistological techniques enabled a substantially more reliable diagnosis of inflammatory cardiomyopathy (DCMi) in endomyocardial biopsies (EMB) compared to the histological Dallas criteria. Decisive progress has been made in the understanding of cellular immune mechanisms in DCMi using immunohistological techniques, which apart from the field of diagnosis refinement have had prognostic implications and an influence on the selection criteria of DCMi patients who will likely benefit from immunosuppressive treatment. Digital image analysis systems have been employed to standardize quantification of immunohistological EMB stainings. Quantification of T cell-related genes by a methodologically validated preamplified real-time RT-PCR revealed that the T cells are characterized by differential expression of Th1-, Treg-, and CTL-related markers, while no major role could be confirmed for Th17 cells. The reported virus-associated differential T cell receptor Vbeta dominance suggests an antiviral specificity of virus-induced T cell responses in human DCMi.

Zusammenfassung

Durch die Einführung immunhistologischer Techniken ist die Diagnostik der inflammatorischen Kardiomyopathie (DCMi) bei Endomyokardbiopsien (EMB) im Vergleich zu den Dallas-Kriterien deutlich verlässlicher geworden. Ein entscheidender Fortschritt im Verständnis der zellulären Immunmechanismen wurde durch die Immunhistologie ermöglicht und hat neben der verbesserten Diagnostik zu prognostischen Implikationen und zu neuen Selektionskriterien für jene DCMi-Patienten geführt, die von einer Immunsuppression profitieren könnten. Ein digitales Bildanalysesystem wurde zur standardisierten Quantifizierung der Immunhistologie von EMB etabliert. Die Quantifizierung von T-Zell-Genen mittels einer methodisch validierten präamplifizierten Echtzeit-Reverse-Transkriptase-Polymerasekettenreaktion zeigte, dass die T-Zell-Infiltrate bei DCMi durch eine differenzielle Expression von Th1, regulatorische und zytotoxische T-Zellen charakterisierenden Markern gekennzeichnet sind, während Th17-Zellen nicht erhöht nachweisbar sind. Die beobachteten Dominanzen von T-Zell-Rezeptor-Vbeta-Familien sind mit einer antiviralen Antigenspezifität der T-Zell-Antwort bei DCMi vereinbar.

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Acknowledgments

This work was supported by the UKGM Foundation (project: 10/2009 MR) to M.N. and B.M.

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On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Cardiology, Faculty of Medicine, University Hospital of Marburg and Giessen/UKGM GmbH, Philipps-Universität Marburg, Baldinger Str. 1, 35043, Marburg, Germany

    M. Noutsias FESC, V.J. Patil & B. Maisch

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  1. M. Noutsias FESC
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  2. V.J. Patil
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  3. B. Maisch
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Correspondence to M. Noutsias FESC.

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Noutsias, M., Patil, V. & Maisch, B. Cellular immune mechanisms in myocarditis. Herz 37, 830–835 (2012). https://doi.org/10.1007/s00059-012-3700-3

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