TY  - JOUR
AV  - public
Y1  - 2018/02/23/
EP  - 11
TI  - Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease
PB  - PUBLIC LIBRARY SCIENCE
N2  - INTRODUCTION:
Huntington?s disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification.

METHODS:
A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau).

RESULTS:
52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age-adjustment.

CONCLUSION:
Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.
ID  - discovery10056827
KW  - Science & Technology
KW  -  Multidisciplinary Sciences
KW  -  Science & Technology - Other Topics
KW  -  GENE CARRIERS
KW  -  MICROGLIAL ACTIVATION
KW  -  NEUROINFLAMMATION
KW  -  PATHOLOGY
KW  -  BIOMARKERS
KW  -  ASTROCYTE
KW  -  PROTEIN
KW  -  YKL-40
KW  -  ONSET
KW  -  MODEL
VL  - 13
IS  - 2
N1  - : © 2018 Niemela¨ et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
UR  - http://dx.doi.org/10.1371/journal.pone.0193492
SN  - 1932-6203
A1  - Niemela, V
A1  - Burman, J
A1  - Blennow, K
A1  - Zetterberg, H
A1  - Larsson, A
A1  - Sundblom, J
JF  - PLoS One
ER  -