Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis
Marco Gallus, Wolfgang Roll, Andre Dik, Cristina Barca, Bastian Zinnhardt, Gordon Hicking, Christoph Mueller, Venu Narayanan Naik, Max Anstötz, Julia Krämer, Leoni Rolfes, Lydia Wachsmuth, Julika Pitsch, Karen M. J. van Loo, Saskia Räuber, Hideho Okada, Catriona Wimberley, Christine Strippel, Kristin S. Golombeck, Andreas Johnen, Stjepana Kovac, Catharina C. Groß, Philipp Backhaus, Robert Seifert, Jan Lewerenz, Rainer Surges, Christian E. Elger, Heinz Wiendl, Tobias Ruck, Albert J. Becker, Cornelius Faber, Andreas H. Jacobs, Jan Bauer, Sven G. Meuth, Michael Schäfers, Nico Melzer
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 [ 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.