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

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A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. / Björkqvist, Maria; Wild, Edward J; Thiele, Jenny; Silvestroni, Aurelio; Andre, Ralph; Lahiri, Nayana; Raibon, Elsa; Lee, Richard V; Benn, Caroline L; Soulet, Denis; Magnusson-Lind, Anna; Woodman, Ben; Landles, Christian; Pouladi, Mahmoud A; Hayden, Michael R; Khalili-Shirazi, Azadeh; Lowdell, Mark W; Brundin, Patrik; Bates, Gillian P; Leavitt, Blair R; Möller, Thomas; Tabrizi, Sarah J.

In: Journal of Experimental Medicine, Vol. 205, 2008, p. 1869-1877.

Research output: Contribution to journalArticle

Harvard

Björkqvist, M, Wild, EJ, Thiele, J, Silvestroni, A, Andre, R, Lahiri, N, Raibon, E, Lee, RV, Benn, CL, Soulet, D, Magnusson-Lind, A, Woodman, B, Landles, C, Pouladi, MA, Hayden, MR, Khalili-Shirazi, A, Lowdell, MW, Brundin, P, Bates, GP, Leavitt, BR, Möller, T & Tabrizi, SJ 2008, 'A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.', Journal of Experimental Medicine, vol. 205, pp. 1869-1877. https://doi.org/10.1084/jem.20080178

APA

CBE

Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, Raibon E, Lee RV, Benn CL, Soulet D, Magnusson-Lind A, Woodman B, Landles C, Pouladi MA, Hayden MR, Khalili-Shirazi A, Lowdell MW, Brundin P, Bates GP, Leavitt BR, Möller T, Tabrizi SJ. 2008. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. Journal of Experimental Medicine. 205:1869-1877. https://doi.org/10.1084/jem.20080178

MLA

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Björkqvist, Maria ; Wild, Edward J ; Thiele, Jenny ; Silvestroni, Aurelio ; Andre, Ralph ; Lahiri, Nayana ; Raibon, Elsa ; Lee, Richard V ; Benn, Caroline L ; Soulet, Denis ; Magnusson-Lind, Anna ; Woodman, Ben ; Landles, Christian ; Pouladi, Mahmoud A ; Hayden, Michael R ; Khalili-Shirazi, Azadeh ; Lowdell, Mark W ; Brundin, Patrik ; Bates, Gillian P ; Leavitt, Blair R ; Möller, Thomas ; Tabrizi, Sarah J. / A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. In: Journal of Experimental Medicine. 2008 ; Vol. 205. pp. 1869-1877.

RIS

TY - JOUR

T1 - A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.

AU - Björkqvist, Maria

AU - Wild, Edward J

AU - Thiele, Jenny

AU - Silvestroni, Aurelio

AU - Andre, Ralph

AU - Lahiri, Nayana

AU - Raibon, Elsa

AU - Lee, Richard V

AU - Benn, Caroline L

AU - Soulet, Denis

AU - Magnusson-Lind, Anna

AU - Woodman, Ben

AU - Landles, Christian

AU - Pouladi, Mahmoud A

AU - Hayden, Michael R

AU - Khalili-Shirazi, Azadeh

AU - Lowdell, Mark W

AU - Brundin, Patrik

AU - Bates, Gillian P

AU - Leavitt, Blair R

AU - Möller, Thomas

AU - Tabrizi, Sarah J

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20080178

DO - 10.1084/jem.20080178

M3 - Article

VL - 205

SP - 1869

EP - 1877

JO - Journal of Experimental Medicine

T2 - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

ER -