{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland"
      ],
      "name": "Venla Ahola"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Maija Saraste"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Marjo Nylund"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland"
      ],
      "name": "Markus Matilainen"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Amelie Luoma"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Anna Vuorimaa"
    },
    {
      "affiliations": [
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Jussi Lehto"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Sini Laaksonen"
    },
    {
      "affiliations": [
        "Department of Life Technologies, Division of Biotechnology, University of Turku, Turku, Finland"
      ],
      "name": "Eeva-Christine Brockmann"
    },
    {
      "affiliations": [
        "Department of Neurology, University Hospital and University of Basel, Basel, Switzerland",
        "Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland"
      ],
      "name": "Jens Kuhle"
    },
    {
      "affiliations": [
        "Department of Neurology, University Hospital and University of Basel, Basel, Switzerland",
        "Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland"
      ],
      "name": "David Leppert"
    },
    {
      "affiliations": [
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Department of Life Technologies, Division of Biotechnology, University of Turku, Turku, Finland"
      ],
      "name": "Tero Soukka"
    },
    {
      "affiliations": [
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Department of Life Technologies, Division of Biotechnology, University of Turku, Turku, Finland"
      ],
      "name": "Urpo Lamminmäki"
    },
    {
      "affiliations": [
        "Clinical Neurosciences, University of Turku, Turku, Finland",
        "Turku PET Centre, University of Turku, Turku University Hospital, and Åbo Akademi University, Turku, Finland",
        "InFLAMES Research Flagship, University of Turku, Turku, Finland",
        "Neurocenter, Turku University Hospital, Turku, Finland"
      ],
      "name": "Laura Airas"
    }
  ],
  "title": "Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis",
  "uid": "4df9ff7a-89cf-5909-bafd-f8bfdce10c31"
}