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<jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate the classifier performance, clinical and biochemical correlations of cerebrospinal fluid (CSF) levels of the chitinase proteins Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1) and Chitinase-3-like protein 2 (CHI3L2) in amyotrophic lateral sclerosis (ALS).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>CSF levels of CHIT1, CHI3L1, CHI3L2, phosphorylated neurofilament heavy chain (pNFH) and C-reactive protein were measured by ELISA in a longitudinal cohort of patients with ALS (n=82), primary lateral sclerosis (PLS, n=10), ALS-mimic conditions (n=12), healthy controls (n=25) and asymptomatic carriers of ALS-causing genetic mutations (AGC; n=5).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p&lt;0.001) and ALS-mimics (CHIT1, p&lt;0.001; CHI3L1, p=0.017; CHI3L2, p&lt;0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p&lt;0.001). Chitinase levels were similar in AGCs and healthy controls. Chitinase proteins distinguished ALS from healthy controls (area under the curve (AUC): CHIT1 0.92; CHI3L1 0.80; CHI3L2 0.90), mimics (AUC: CHIT1 0.84; CHI3L1 0.73; CHI3L2 0.88) and, to a lesser extent, PLS (AUC: CHIT 0.73; CHI3L1 0.51; CHI3L2 0.82) but did not outperform pNFH. CHIT1 and CHI3L2 correlated with disease progression rate (Pearson’s <jats:italic>r</jats:italic>=0.49, p&lt;0.001; <jats:italic>r</jats:italic>=0.42, p&lt;0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (<jats:italic>r</jats:italic>=−0.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>CSF chitinase proteins may have limited value as independent diagnostic and stratification biomarkers in ALS, but offer a window into non-autonomous mechanisms of motor neuronal loss in ALS, specifically in assessing response to therapies targeting neuroinflammatory pathways.</jats:p></jats:sec>

Original publication

DOI

10.1136/jnnp-2019-320442

Type

Journal article

Journal

Journal of Neurology, Neurosurgery & Psychiatry

Publisher

BMJ

Publication Date

11/2019

Volume

90

Pages

1215 - 1220