Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis.

BACKGROUND AND PURPOSE: The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins is yet to be established. Our objective was to investigate the potential of chitinase 3-like 2 (CHI3L2) and chitotriosidase as prognostic biomarkers in optic neuritis (ON) as the first demyelinating episode and to evaluate the ability of CHI3L2 to predict long-term MS risk and disability. METHODS: In a prospective cohort of 73 patients with ON as a first demyelinating episode and 26 age-matched healthy controls levels of CHI3L2 and chitotriosidase in CSF were explored by enzyme-linked immunosorbent assay. Associations with magnetic resonance imaging white matter lesions, CSF oligoclonal bands, immunoglobulin G index and leukocyte count were investigated. Long-term MS risk and disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite components) were examined in a retrospective cohort of 78 patients with ON as the first demyelinating episode (mean follow-up 14 years). The predictive ability of CHI3L2 was compared with CHI3L1. RESULTS: Cerebrospinal fluid levels of CHI3L2 and chitotriosidase were significantly elevated in patients with ON and were associated with MS risk measures. CHI3L2 levels predicted MS development after ON (hazard ratio 1.95, P = 0.00039, Cox regression) and cognitive impairment by the Paced Auditory Serial Addition Test (P = 0.0357, linear regression) at follow-up. In a multivariate analysis of MS risk, CHI3L2 performed better than CHI3L1. CONCLUSIONS: CHI3L2 and chitotriosidase are promising biomarkers in patients with a first demyelinating episode. Our findings thus support a role for these proteins as biomarkers in early MS.

Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis.

BACKGROUND: Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. OBJECTIVE: The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis. METHODS: We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses. RESULTS: CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (ß=13.8, p=0.0008), RNFL (ß=5.6, p=0.0004) and GC-IPL (ß=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (ß=12.9, p=0.0021 for NF-L, ß=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission. CONCLUSION: CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.

Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed. OBJECTIVE: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON). METHODS: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6-19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used. RESULTS: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI (p=0.0001), chitinase 3-like 1 (p=0.0033) and age (p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale (p=0.0111) and nine-hole-peg-test (p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test (p=0.0150). CONCLUSION: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.