eprintid: 1354397
rev_number: 60
eprint_status: archive
userid: 608
dir: disk0/01/35/43/97
datestamp: 2012-08-01 18:36:59
lastmod: 2021-09-18 21:48:13
status_changed: 2012-08-01 18:36:59
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Weiss, A
creators_name: Träger, U
creators_name: Wild, EJ
creators_name: Grueninger, S
creators_name: Farmer, R
creators_name: Landles, C
creators_name: Scahill, RI
creators_name: Lahiri, N
creators_name: Haider, S
creators_name: Macdonald, D
creators_name: Frost, C
creators_name: Bates, GP
creators_name: Bilbe, G
creators_name: Kuhn, R
creators_name: Andre, R
creators_name: Tabrizi, SJ
title: Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F77
divisions: F86
keywords: Atrophy, B-Lymphocytes, Biological Markers, Blotting, Western, Caudate Nucleus, Disease Progression, Fluorescence Resonance Energy Transfer, Humans, Huntington Disease, Immunoprecipitation, Leukocytes, Monocytes, Mutation, Nerve Tissue Proteins, T-Lymphocytes
note: PMCID: PMC3461928
abstract: Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin (HTT). Therapeutic approaches to lower mutant HTT (mHTT) levels are expected to proceed to human trials, but noninvasive quantification of mHTT is not currently possible. The importance of the peripheral immune system in neurodegenerative disease is becoming increasingly recognized. Peripheral immune cells have been implicated in HD pathogenesis, but HTT levels in these cells have not been quantified before. A recently described time-resolved Förster resonance energy transfer (TR-FRET) immunoassay was used to quantify mutant and total HTT protein levels in leukocytes from patients with HD. Mean mHTT levels in monocytes, T cells, and B cells differed significantly between patients with HD and controls and between pre-manifest mutation carriers and those with clinical onset. Monocyte and T cell mHTT levels were significantly associated with disease burden scores and caudate atrophy rates in patients with HD. mHTT N-terminal fragments detected in HD PBMCs may explain the progressive increase in mHTT levels in these cells. These findings indicate that quantification of mHTT in peripheral immune cells by TR-FRET holds significant promise as a noninvasive disease biomarker.
date: 2012-10-01
official_url: http://dx.doi.org/10.1172/JCI64565
vfaculties: VFBRS
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article, Research Support, Non-U.S. Gov't
verified: verified_manual
elements_source: PubMed
elements_id: 424516
doi: 10.1172/JCI64565
pii: 64565
lyricists_name: Andre, Ralph
lyricists_name: Bates, Gillian
lyricists_name: Haider, Salman
lyricists_name: Lahiri, Nayana
lyricists_name: Landles, Christian
lyricists_name: Scahill, Rachael
lyricists_name: Tabrizi, Sarah
lyricists_name: Traeger, Ulrike
lyricists_name: Wild, Edward
lyricists_id: RANDR07
lyricists_id: GBATE91
lyricists_id: SHAID10
lyricists_id: NLAHI34
lyricists_id: CLAND22
lyricists_id: RSCAH26
lyricists_id: SJTAB21
lyricists_id: USCHU63
lyricists_id: EJWIL36
full_text_status: public
publication: Journal of Clinical Investigation
volume: 122
number: 10
pagerange: 3731 - 3736
event_location: United States
issn: 0021-9738
citation:        Weiss, A;    Träger, U;    Wild, EJ;    Grueninger, S;    Farmer, R;    Landles, C;    Scahill, RI;                                     ... Tabrizi, SJ; + view all <#>        Weiss, A;  Träger, U;  Wild, EJ;  Grueninger, S;  Farmer, R;  Landles, C;  Scahill, RI;  Lahiri, N;  Haider, S;  Macdonald, D;  Frost, C;  Bates, GP;  Bilbe, G;  Kuhn, R;  Andre, R;  Tabrizi, SJ;   - view fewer <#>    (2012)    Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression.                   Journal of Clinical Investigation , 122  (10)   3731 - 3736.    10.1172/JCI64565 <https://doi.org/10.1172/JCI64565>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1354397/1/JCI64565.pdf