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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
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.
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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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