CSF chitinase proteins in amyotrophic lateral sclerosis
<p>Objective: 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...
| Main Authors: | , , , , , |
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| Format: | Journal article |
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BMJ Publishing Group
2019
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| _version_ | 1826279836314763264 |
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| author | Thompson, A Gray, E Bampton, A Raciborska, D Talbot, K Turner, M |
| author_facet | Thompson, A Gray, E Bampton, A Raciborska, D Talbot, K Turner, M |
| author_sort | Thompson, A |
| collection | OXFORD |
| description | <p>Objective: 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).</p> <p>Methods: 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).</p> <p>Results: CSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p<0.001) and ALS-mimics (CHIT1, p<0.001; CHI3L1, p=0.017; CHI3L2, p<0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p<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 r=0.49, p<0.001; r=0.42, p<0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (r=−0.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable.</p> <p>Conclusions: 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.</p> |
| first_indexed | 2024-03-07T00:04:44Z |
| format | Journal article |
| id | oxford-uuid:772aa7ff-376e-4545-af09-5541125fe3e6 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:04:44Z |
| publishDate | 2019 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:772aa7ff-376e-4545-af09-5541125fe3e62022-03-26T20:21:54ZCSF chitinase proteins in amyotrophic lateral sclerosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:772aa7ff-376e-4545-af09-5541125fe3e6Symplectic Elements at OxfordBMJ Publishing Group2019Thompson, AGray, EBampton, ARaciborska, DTalbot, KTurner, M<p>Objective: 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).</p> <p>Methods: 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).</p> <p>Results: CSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p<0.001) and ALS-mimics (CHIT1, p<0.001; CHI3L1, p=0.017; CHI3L2, p<0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p<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 r=0.49, p<0.001; r=0.42, p<0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (r=−0.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable.</p> <p>Conclusions: 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.</p> |
| spellingShingle | Thompson, A Gray, E Bampton, A Raciborska, D Talbot, K Turner, M CSF chitinase proteins in amyotrophic lateral sclerosis |
| title | CSF chitinase proteins in amyotrophic lateral sclerosis |
| title_full | CSF chitinase proteins in amyotrophic lateral sclerosis |
| title_fullStr | CSF chitinase proteins in amyotrophic lateral sclerosis |
| title_full_unstemmed | CSF chitinase proteins in amyotrophic lateral sclerosis |
| title_short | CSF chitinase proteins in amyotrophic lateral sclerosis |
| title_sort | csf chitinase proteins in amyotrophic lateral sclerosis |
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