eprintid: 10056827 rev_number: 18 eprint_status: archive userid: 608 dir: disk0/10/05/68/27 datestamp: 2018-09-24 11:30:12 lastmod: 2021-10-03 23:54:23 status_changed: 2018-09-24 11:30:12 type: article metadata_visibility: show creators_name: Niemela, V creators_name: Burman, J creators_name: Blennow, K creators_name: Zetterberg, H creators_name: Larsson, A creators_name: Sundblom, J title: Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, GENE CARRIERS, MICROGLIAL ACTIVATION, NEUROINFLAMMATION, PATHOLOGY, BIOMARKERS, ASTROCYTE, PROTEIN, YKL-40, ONSET, MODEL note: : © 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. 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. 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. date: 2018-02-23 date_type: published publisher: PUBLIC LIBRARY SCIENCE official_url: http://dx.doi.org/10.1371/journal.pone.0193492 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1541283 doi: 10.1371/journal.pone.0193492 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: PLoS One volume: 13 number: 2 pages: 11 issn: 1932-6203 citation: Niemela, V; Burman, J; Blennow, K; Zetterberg, H; Larsson, A; Sundblom, J; (2018) Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease. PLoS One , 13 (2) 10.1371/journal.pone.0193492 <https://doi.org/10.1371/journal.pone.0193492>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10056827/1/journal.pone.0193492.pdf