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Objective  To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS).    Methods  We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer's instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up.    Results  Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118–0.742,  p  = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063–0.725,  p  = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999–1.017,  p  = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = −0.366, 95% CI -0.676–0.054,  p  = 0.086). There was no correlation with regard to NfL levels.    Conclusions  This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved.    Classification of evidence  This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.

CSF chitinase 3-like-1 association with disability of primary progressive MS