Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Early Intrathecal T Helper 17.1 Cell Activity in Huntington Disease

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. MRI in Neuromuscular Diseases: An Emerging Diagnostic Tool and Biomarker for Prognosis and Efficacy

    Research output: Contribution to journalReviewResearchpeer-review

  2. A New Glycogen Storage Disease Caused by a Dominant PYGM Mutation

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Neuroinflammatory markers associate with cognitive decline after major surgery: findings of an explorative study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Hypersensitivity to Calcitonin Gene-Related Peptide in Post-Traumatic Headache

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Mania triggered by levodopa treatment in a patient with frontotemporal dementia caused by A C9orf72 repeat expansion: A case report

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Glutamate-glutamine homeostasis is perturbed in neurons and astrocytes derived from patient iPSC models of frontotemporal dementia

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Enhancement of Autophagy and Solubilization of Ataxin-2 Alleviate Apoptosis in Spinocerebellar Ataxia Type 2 Patient Cells

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

OBJECTIVE: Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. No disease-modifying therapy exists for the treatment of patients with HD. The purpose of this study was therefore to investigate early disease mechanisms that potentially could be used as a target therapeutically.

METHODS: Lymphocyte activity in cerebrospinal fluid (CSF) from 4 cohorts of HTT gene expansion carriers (n = 121 in total) and controls was analyzed by techniques based on flow cytometry and enzyme-linked immunosorbent assays.

RESULTS: The data of this study provide evidence of immune abnormalities before motor onset of disease. In CSF of HTT gene expansion carriers, we found increased levels of proinflammatory cytokines, including IL-17, and increased consumption of the lymphocyte growth factor IL-7 before motor onset of HD. In concordance, we observed an increased prevalence of IL-17-producing Th17.1 cells in the CSF of HTT gene expansion carriers, predominantly in pre-motor manifest individuals. The frequency of intrathecal Th17.1 cells correlated negatively with progression of HD and the level of neurodegeneration, suggesting a role of Th17.1 cells in the early disease stage. We also observed a skewing in the balance between proinflammatory and regulatory T cells potentially favoring a proinflammatory intrathecal environment in HTT gene expansion carriers.

INTERPRETATION: These data suggest that Th17.1 cells are implicated in the earliest pathogenic phases of HD and suggest that treatment to dampen T -cell-driven inflammation before motor onset might be of benefit in HTT gene expansion carriers. ANN NEUROL 2019.

Original languageEnglish
JournalAnnals of Neurology
Volume87
Issue number2
Pages (from-to)246-255
Number of pages10
ISSN0364-5134
DOIs
Publication statusPublished - 1 Feb 2020

ID: 58652565