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Multiplex quantitative imaging of human myocardial infarction by mass spectrometry-immunohistochemistry

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Abstract

Simultaneous assessment of a panel of protein markers is becoming essential in order to enhance biomarker research and improve diagnostics. Specifically, postmortem diagnostics of early myocardial ischemia in sudden cardiac death cases could benefit from a multiplex marker assessment in the same tissue section. Current analytical antibody-based techniques (immunohistochemistry and immunofluorescence) limit multiplex analysis usually to not more than three antibodies. In this study, mass spectrometry-immunohistochemistry (MS-IHC) was performed by combining laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) with rare-metal-isotope-tagged antibodies as a technique for multiplex analysis of human postmortem myocardial tissue samples. Tissue sections with myocardial infarction were simultaneously analyzed for seven primary, rare-metal-isotope-tagged antibodies (troponin T, myoglobin, fibronectin, C5b-9, unphosphorylated connexin 43, VEGF-B, and JunB). Comparison between the MS-IHC approach and chromogenic IHC showed similar patterns in ionic and optical images. In addition, absolute quantification was performed by MS-IHC, providing a proportional relationship between the signal intensity and the local marker concentration in tissue sections. These data demonstrated that LA-ICP-MS combined with rare-metal-isotope-tagged antibodies is an efficient strategy for simultaneous testing of multiple markers and allows not only visualization of molecules within the tissue but also quantification of the signal. Such imaging approach has a great potential in both diagnostics and pathology-related research.

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Acknowledgements

We would like to thank Max Villa and Catia Pomponio for the support and assistance with LA-ICP-MS and immunohistochemistry, respectively.

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Authors and Affiliations

  1. University Center of Legal Medicine, Lausanne-Geneva, Rue Michel-Servet, 11211, Geneva, Switzerland

    Aleksandra Aljakna, Estelle Lauer, Sébastien Lenglet, Silke Grabherr, Tony Fracasso, Marc Augsburger, Sara Sabatasso & Aurélien Thomas

  2. Faculty of Biology and Medicine, University of Lausanne, Vulliette 04, 1000, Lausanne 25, Switzerland

    Aurélien Thomas

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  1. Aleksandra Aljakna
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Correspondence to Aurélien Thomas.

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The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, formal consent is not required. All cases included in this study were obtained from the autopsy database in our center. In agreement with the local ethics committee and the local general prosecutor, these cases can be included in this type of studies, provided that they are anonymized. In this investigation, no information allowing the identification of a person is given. People, who had previously refused, in a written form, their consent to bequeath their body parts for research use, were excluded from the study.

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Aljakna, A., Lauer, E., Lenglet, S. et al. Multiplex quantitative imaging of human myocardial infarction by mass spectrometry-immunohistochemistry. Int J Legal Med 132, 1675–1684 (2018). https://doi.org/10.1007/s00414-018-1813-9

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