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

Gallus M; Roll W; Dik A; Barca C; Zinnhardt B; Hicking G; Mueller C; Naik VN; Anstötz M; Krämer J; Rolfes L; Wachsmuth L; Pitsch J; van Loo KMJ; Räuber S; Okada H; Wimberley C; Strippel C; Golombeck KS; Johnen A; Kovac S; Groß CC; Backhaus P; Seifert R; Lewerenz J; Surges R; Elger CE; Wiendl H; Ruck T; Becker AJ; Faber C; Jacobs AH; Bauer J; Meuth SG; Schäfers M; Melzer N

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.