A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.

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Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.


  • Edward J Wild
  • Jenny Thiele
  • Aurelio Silvestroni
  • Ralph Andre
  • Nayana Lahiri
  • Elsa Raibon
  • Richard V Lee
  • Caroline L Benn
  • Denis Soulet
  • Anna Magnusson-Lind
  • Ben Woodman
  • Christian Landles
  • Mahmoud A Pouladi
  • Michael R Hayden
  • Azadeh Khalili-Shirazi
  • Mark W Lowdell
  • Patrik Brundin
  • Gillian P Bates
  • Blair R Leavitt
  • Thomas Möller
  • Sarah J Tabrizi
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
  • Medicinska grundvetenskaper
Sidor (från-till)1869-1877
TidskriftJournal of Experimental Medicine
StatusPublished - 2008
Peer review utfördJa