Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis

TSPO 的转化成像揭示了人类和鼠 CD8 T 细胞介导的边缘叶脑炎中明显的先天性炎症

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作者: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

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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