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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.
Afiliação
  • Gallus M; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Roll W; Department of Neurosurgery, University of Münster, Münster, Germany.
  • Dik A; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA.
  • Barca C; Department of Nuclear Medicine, University of Münster, Münster, Germany.
  • Zinnhardt B; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Hicking G; Department of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
  • Mueller C; European Institute for Molecular Imaging, University of Münster, Münster, Germany.
  • Naik VN; European Institute for Molecular Imaging, University of Münster, Münster, Germany.
  • Anstötz M; Biomarkers and Translational Technologies (BTT), Pharma Research and Early Development (pRED), F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Krämer J; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Rolfes L; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Wachsmuth L; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Pitsch J; Institute of Anatomy II, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
  • van Loo KMJ; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Räuber S; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Okada H; Department of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
  • Wimberley C; Department of Clinical Radiology, University of Münster, Münster, Germany.
  • Strippel C; Department of Epileptology, University of Bonn, Bonn, Germany.
  • Golombeck KS; Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn, Bonn, Germany.
  • Johnen A; Department of Epileptology and Neurology, RWTH Aachen University, Aachen, Germany.
  • Kovac S; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Groß CC; Department of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
  • Backhaus P; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA.
  • Seifert R; Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.
  • Lewerenz J; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Surges R; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Elger CE; Department of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
  • Wiendl H; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Ruck T; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Becker AJ; Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Faber C; Department of Nuclear Medicine, University of Münster, Münster, Germany.
  • Jacobs AH; European Institute for Molecular Imaging, University of Münster, Münster, Germany.
  • Bauer J; Department of Nuclear Medicine, University of Münster, Münster, Germany.
  • Meuth SG; European Institute for Molecular Imaging, University of Münster, Münster, Germany.
  • Schäfers M; Department of Neurology, University of Ulm, Ulm, Germany.
  • Melzer N; Department of Epileptology, University of Bonn, Bonn, Germany.
Sci Adv ; 9(23): eabq7595, 2023 06 09.
Article em En | MEDLINE | ID: mdl-37294768
ABSTRACT
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 [18F]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 [18F]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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encefalite Límbica Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encefalite Límbica Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha