Department of Neurology Institute of Translational Neurology, University of Münster, Münster, Germany.
Department of Neurosurgery, University of Münster, Münster, Germany.
Sci Adv. 2023 Jun 9;9(23):eabq7595. doi: 10.1126/sciadv.abq7595.
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 [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 [F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell-mediated ALE.
自身免疫性边缘性脑炎（ALE）表现为新发性内侧颞叶癫痫、进行性记忆障碍以及其他行为和认知改变。CD8 T 细胞被认为在自身抗体（ABs）针对细胞内抗原或未发现 ABs 的情况下发挥关键作用。评估这些患者具有临床挑战性，迫切需要新的非侵入性成像生物标志物。在这里，我们证明使用 [F]DPA-714-PET-MRI 可视化转位蛋白（TSPO）可在疑似 CD8 T 细胞 ALE 患者的海马体和杏仁核中显示出明显的小胶质细胞激活和反应性神经胶质增生，与 FLAIR-MRI 和 EEG 改变相关。将这些转化数据反向翻译到神经元抗原特异性 CD8 T 细胞介导的 ALE 的临床前小鼠模型中，使我们能够证实我们的初步临床发现。这些转化数据强调了 [F]DPA-714-PET-MRI 作为一种临床分子成像方法，可直接评估 CD8 T 细胞介导的 ALE 中的固有免疫。
