Author Of 1 Presentation
P0441 - Cerebrospinal fluid chitinase-3-like protein 1 is associated with disability progression in primary progressive multiple sclerosis (ID 1861)
Abstract
Background
With the arrival of disease modifying treatment for primary progressive multiple sclerosis (PPMS), biomarkers of unfavorable outcome are badly needed. Neuropathologically, PPMS is characterized by diffuse and compartmentalized low-grade inflammation with microglial activation. A microglia-related marker, cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1), was shown to predict disability progression in relapsing-remitting MS, but has not been studied extensively in progressive forms of disease.
Objectives
We aimed to evaluate the prognostic potential of CSF biomarkers reflecting microglial activation (CHI3L) and neuroaxonal damage (neurofilaments light chain, NFL) in our cohort of PPMS patients.
Methods
Thirty-eight PPMS patients (24 women) with median age of 54 years (range 34,5 – 72,9 years) were admitted to our department between 2013-2020. They presented with a median 3-years (range 0.5-30-year) history of spastic paraparesis and had basic CSF analysis with CSF cell count, albumin quotient, oligoclonal bands (OCB) and quantitative IgG and IgM synthesis done at the time of diagnosis. One-year follow-up data with Extended Disability Status Scale (EDSS) were available for 30 patients. CSF CHI3L1 and NFL were measured by enzyme-linked immunosorbent assays (Quantikine ELISA kit, R&D Systems Inc. and UmanDiagnostics AB, respectively). The Spearman’s rho test was used to test for associations between CSF biomarkers and disability progression.
Results
All patients had typical brain MRI lesions (74% more than 10, 83% also spinal cord lesions) and in 90% OCB were detected. At follow-up, nearly one half (n=14) of the patients showed EDSS progression of at least 0.5 points. Despite the correlation between CSF CHI3L1 and NFL levels (ρ = 0.543, p < 0.01), CHI3L1, but not NFL, was significantly higher in patients with EDSS progression (176 ng/ml vs. 235 ng/ml, p < 0.01) and correlated with one-year EDSS change (ρ = 0.407, p = 0.025). A moderate negative correlation between CHI3L1 and disease duration was also observed (ρ = -0.370, p = 0.02) as well as association with CSF cell count and IgG intrathecal synthesis (ρ = 0.465, p < 0.01). CHI3L1 was not related with the number of MRI lesions at the time of diagnosis.
Conclusions
CHI3L1 was associated with disease duration and disability progression in PPMS patients. Its prognostic biomarker potential for this disabling form of MS should be further studied in a larger, prospective study cohort.