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Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease

Journal article
Authors V. Niemela
J. Burman
Kaj Blennow
Henrik Zetterberg
A. Larsson
J. Sundblom
Published in Plos One
Volume 13
Issue 2
ISSN 1932-6203
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Links https://doi.org/10.1371/journal.pon...
Keywords gene carriers, microglial activation, neuroinflammation, pathology, biomarkers, astrocyte, protein, ykl-40, onset, model, Science & Technology - Other Topics
Subject categories Neurochemistry, Psychiatry

Abstract

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. 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). 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. 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.

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