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

Björkqvist, Maria LU ; Wild, Edward J; Thiele, Jenny; Silvestroni, Aurelio; Andre, Ralph; Lahiri, Nayana; Raibon, Elsa; Lee, Richard V; Benn, Caroline L and Soulet, Denis LU , et al. (2008) In Journal of Experimental Medicine 205. p.1869-1877
Abstract
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... (More)
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. (Less)
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publication status
published
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Journal of Experimental Medicine
volume
205
pages
1869 - 1877
publisher
Rockefeller University Press
external identifiers
  • WOS:000258528500016
  • PMID:18625748
  • Scopus:49249089029
ISSN
1540-9538
DOI
10.1084/jem.20080178
language
English
LU publication?
yes
id
881d9242-1fc3-4e78-8ebc-95cd7e02bae8 (old id 1181132)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18625748?dopt=Abstract
date added to LUP
2008-08-08 15:47:49
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2016-12-04 04:40:38
@misc{881d9242-1fc3-4e78-8ebc-95cd7e02bae8,
  abstract     = {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.},
  author       = {Björkqvist, Maria and Wild, Edward J and Thiele, Jenny and Silvestroni, Aurelio and Andre, Ralph and Lahiri, Nayana and Raibon, Elsa and Lee, Richard V and Benn, Caroline L and Soulet, Denis and Magnusson-Lind, Anna and Woodman, Ben and Landles, Christian and Pouladi, Mahmoud A and Hayden, Michael R and Khalili-Shirazi, Azadeh and Lowdell, Mark W and Brundin, Patrik and Bates, Gillian P and Leavitt, Blair R and Möller, Thomas and Tabrizi, Sarah J},
  issn         = {1540-9538},
  language     = {eng},
  pages        = {1869--1877},
  publisher    = {ARRAY(0xb41cbd8)},
  series       = {Journal of Experimental Medicine},
  title        = {A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.},
  url          = {http://dx.doi.org/10.1084/jem.20080178},
  volume       = {205},
  year         = {2008},
}