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

Authors :
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
Source :
Science advances [Sci Adv] 2023 Jun 09; Vol. 9 (23), pp. eabq7595. Date of Electronic Publication: 2023 Jun 09.
Publication Year :
2023

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 [ <superscript>18</superscript> 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 [ <superscript>18</superscript> F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell-mediated ALE.

Details

Language :
English
ISSN :
2375-2548
Volume :
9
Issue :
23
Database :
MEDLINE
Journal :
Science advances
Publication Type :
Academic Journal
Accession number :
37294768
Full Text :
https://doi.org/10.1126/sciadv.abq7595