Abstract
Background: Evidence supports that neurodevelopmental diseases, such as Tourette syndrome (TS), may involve dysfunctional neural-immune crosstalk. This could lead to altered brain maturation and differences in immune and stress responses. Dendritic cells (DCs) play a major role in immunity as professional antigen-presenting cells; changes in their frequency have been observed in several autoimmune conditions.
Methods: In 18 TS patients (15 on stable pharmacological treatment, three unmedicated) and 18 age-matched healthy volunteers (HVs), we explored circulating blood-derived DCs and their relationship with clinical variables and brain metabolites, measured via proton magnetic resonance spectroscopy (1H-MRS). DC subsets, including plasmacytoid and myeloid type 1 and 2 dendritic cells (MDC1, MDC2), were studied with flow cytometry. 1H-MRS was used to measure total choline, glutamate plus glutamine, total creatine (tCr), and total N-acetylaspartate and N-acetylaspartyl-glutamate levels in frontal white matter (FWM) and the putamen.
Results: We did not observe differences in absolute concentrations of DC subsets or brain inflammatory metabolites between patients and HVs. However, TS patients manifesting anxiety showed a significant increase in MDC1s compared to TS patients without anxiety (p = 0.01). We also found a strong negative correlation between MDC1 frequency and tCr in the FWM of patients with TS (p = 0.0015), but not of HVs.
Conclusion: Elevated frequencies of the MDC1 subset in TS patients manifesting anxiety may reflect a proinflammatory status, potentially facilitating altered neuro-immune crosstalk. Furthermore, the strong inverse correlation between brain tCr levels and MDC1 subset frequency in TS patients suggests a potential association between proinflammatory status and metabolic changes in sensitive brain regions.
Original language | English |
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Pages (from-to) | 1910-1921 |
Number of pages | 12 |
Journal | European Journal of Neurology |
Volume | 28 |
Issue number | 6 |
Early online date | 26 Mar 2021 |
DOIs | |
Publication status | Published - Jun 2021 |
Bibliographical note
Funding Information:This work was supported by a research grant from Stiftung “Immunität und Seele”, Munich, Germany to Dr Davide Martino and Dr Mark J. Edwards.
Publisher Copyright:
© 2021 European Academy of Neurology
Keywords
- anxiety
- dendritic cells
- inflammation
- spectroscopy
- Tourette syndrome
ASJC Scopus subject areas
- Neurology
- Clinical Neurology