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Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis
Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10256169/ https://www.ncbi.nlm.nih.gov/pubmed/37294768 http://dx.doi.org/10.1126/sciadv.abq7595 |
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author | Gallus, Marco Roll, Wolfgang Dik, Andre Barca, Cristina Zinnhardt, Bastian Hicking, Gordon Mueller, Christoph Naik, Venu Narayanan Anstötz, Max Krämer, Julia Rolfes, Leoni Wachsmuth, Lydia Pitsch, Julika van Loo, Karen M. J. Räuber, Saskia Okada, Hideho Wimberley, Catriona Strippel, Christine Golombeck, Kristin S. Johnen, Andreas Kovac, Stjepana Groß, Catharina C. Backhaus, Philipp Seifert, Robert Lewerenz, Jan Surges, Rainer Elger, Christian E. Wiendl, Heinz Ruck, Tobias Becker, Albert J. Faber, Cornelius Jacobs, Andreas H. Bauer, Jan Meuth, Sven G. Schäfers, Michael Melzer, Nico |
author_facet | Gallus, Marco Roll, Wolfgang Dik, Andre Barca, Cristina Zinnhardt, Bastian Hicking, Gordon Mueller, Christoph Naik, Venu Narayanan Anstötz, Max Krämer, Julia Rolfes, Leoni Wachsmuth, Lydia Pitsch, Julika van Loo, Karen M. J. Räuber, Saskia Okada, Hideho Wimberley, Catriona Strippel, Christine Golombeck, Kristin S. Johnen, Andreas Kovac, Stjepana Groß, Catharina C. Backhaus, Philipp Seifert, Robert Lewerenz, Jan Surges, Rainer Elger, Christian E. Wiendl, Heinz Ruck, Tobias Becker, Albert J. Faber, Cornelius Jacobs, Andreas H. Bauer, Jan Meuth, Sven G. Schäfers, Michael Melzer, Nico |
author_sort | Gallus, Marco |
collection | PubMed |
description | Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [(18)F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the hippocampus and amygdala of patients suspected with CD8 T cell ALE, which correlates with FLAIR-MRI and EEG alterations. Back-translation into a preclinical mouse model of neuronal antigen-specific CD8 T cell–mediated ALE allowed us to corroborate our preliminary clinical findings. These translational data underline the potential of [(18)F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell–mediated ALE. |
format | Online Article Text |
id | pubmed-10256169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-102561692023-06-10 Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis Gallus, Marco Roll, Wolfgang Dik, Andre Barca, Cristina Zinnhardt, Bastian Hicking, Gordon Mueller, Christoph Naik, Venu Narayanan Anstötz, Max Krämer, Julia Rolfes, Leoni Wachsmuth, Lydia Pitsch, Julika van Loo, Karen M. J. Räuber, Saskia Okada, Hideho Wimberley, Catriona Strippel, Christine Golombeck, Kristin S. Johnen, Andreas Kovac, Stjepana Groß, Catharina C. Backhaus, Philipp Seifert, Robert Lewerenz, Jan Surges, Rainer Elger, Christian E. Wiendl, Heinz Ruck, Tobias Becker, Albert J. Faber, Cornelius Jacobs, Andreas H. Bauer, Jan Meuth, Sven G. Schäfers, Michael Melzer, Nico Sci Adv Biomedicine and Life Sciences Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [(18)F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the hippocampus and amygdala of patients suspected with CD8 T cell ALE, which correlates with FLAIR-MRI and EEG alterations. Back-translation into a preclinical mouse model of neuronal antigen-specific CD8 T cell–mediated ALE allowed us to corroborate our preliminary clinical findings. These translational data underline the potential of [(18)F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell–mediated ALE. American Association for the Advancement of Science 2023-06-09 /pmc/articles/PMC10256169/ /pubmed/37294768 http://dx.doi.org/10.1126/sciadv.abq7595 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Gallus, Marco Roll, Wolfgang Dik, Andre Barca, Cristina Zinnhardt, Bastian Hicking, Gordon Mueller, Christoph Naik, Venu Narayanan Anstötz, Max Krämer, Julia Rolfes, Leoni Wachsmuth, Lydia Pitsch, Julika van Loo, Karen M. J. Räuber, Saskia Okada, Hideho Wimberley, Catriona Strippel, Christine Golombeck, Kristin S. Johnen, Andreas Kovac, Stjepana Groß, Catharina C. Backhaus, Philipp Seifert, Robert Lewerenz, Jan Surges, Rainer Elger, Christian E. Wiendl, Heinz Ruck, Tobias Becker, Albert J. Faber, Cornelius Jacobs, Andreas H. Bauer, Jan Meuth, Sven G. Schäfers, Michael Melzer, Nico Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis |
title | Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis |
title_full | Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis |
title_fullStr | Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis |
title_full_unstemmed | Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis |
title_short | Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis |
title_sort | translational imaging of tspo reveals pronounced innate inflammation in human and murine cd8 t cell–mediated limbic encephalitis |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10256169/ https://www.ncbi.nlm.nih.gov/pubmed/37294768 http://dx.doi.org/10.1126/sciadv.abq7595 |
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