A1 Refereed original research article in a scientific journal
Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis
Authors: Ahola, Venla; Saraste, Maija; Nylund, Marjo; Matilainen, Markus; Luoma, Amelie; Vuorimaa, Anna; Lehto, Jussi; Laaksonen, Sini; Brockmann, Eeva-Christine; Kuhle, Jens; Leppert, David; Soukka, Tero; Lamminmäki, Urpo; Airas, Laura
Publisher: BMJ PUBLISHING GROUP
Publishing place: LONDON
Publication year: 2025
Journal: Journal of Neurology, Neurosurgery and Psychiatry
Journal name in source: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
Journal acronym: J NEUROL NEUROSUR PS
Number of pages: 8
ISSN: 0022-3050
eISSN: 1468-330X
DOI: https://doi.org/10.1136/jnnp-2025-336063
Web address : https://doi.org/10.1136/jnnp-2025-336063
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/498671496
Background Multiple sclerosis (MS) progression independent of relapses is driven by brain innate immune cell activation. The aim of this study was to evaluate the association between chitinase-3-like protein 1 (CHI3L1), expressed in brain by astrocytes and microglia, measured from blood and smouldering inflammation measured using 18 kDa translocator protein (TSPO) positron emission tomography (PET) in patients with MS.
Methods The study cohort included 55 patients with MS (25 progressive MS (PMS) and 30 relapsing remitting MS (RRMS)) and 17 healthy controls (HC). CHI3L1 was measured with commercial ELISA from plasma samples. A subcohort (44 MS and 9 HC) underwent TSPO-PET to assess [11C]PK11195 distribution volume ratio (DVR) and MRI concurrent to blood sampling. These imaging outcomes were used in respective correlation and linear regression analyses.
Results CHI3L1 concentration in plasma was higher in PMS (23.5 ng/mL) compared with HC (16.8 ng/mL, p=0.0055) and RRMS (19.3 ng/mL, p=0.049). CHI3L1 associated with brain [11C]PK11195 DVR in all MS (standardised estimate 0.89, 95% CI 0.23 to 1.55, p=0.010) and in PMS (Spearman correlation ρ=0.58, 95% CI 0.058 to 0.86, p=0.032). Additionally, CHI3L1 was associated with smaller brain volume in both MS (-0.75, -1.38 to -0.11, p=0.023) and PMS (ρ=-0.56, -0.83 to -0.095, p=0.021). Furthermore, CHI3L1 was associated with Expanded Disability Status Scale (0.70, 0.12 to 1.28, p=0.019) and age (0.93, 0.37 to 1.48, p=0.002) among all patients with MS.
Conclusions Association of CHI3L1 with glial activation and brain volume loss identifies plasma CHI3L1 as a promising biomarker for smouldering inflammation and MS progression-related pathology.
Downloadable publication This is an electronic reprint of the original article. |
Funding information in the publication:
This work was supported (salary of Venla Ahola) by ImmuDocs National Doctoral Education Pilot Based on the Immune System (decision number OKM/14/523/2024, Document ID 704155), a grant from the National MS Society and the National Stem Cell Foundation (decision number RFA-2203-39281), The Jane and Aatos Erkko Foundation (decision number #220026) and the InFLAMES Flagship Programme of the Research Council of Finland (decision numbers: 337530, 357910 and 358823).