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

Mult Scler. 2015 Dec;21(14):1761-70. doi: 10.1177/1352458515574148. Epub 2015 Feb 19.


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.

Keywords: Biological markers; CHI3L1 protein; CSF; chitinase; human; multiple sclerosis; neurofilament protein L; optic neuritis; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / cerebrospinal fluid*
  • Adolescent
  • Adult
  • Biomarkers / cerebrospinal fluid
  • Chitinase-3-Like Protein 1
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Lectins / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Neurofilament Proteins / cerebrospinal fluid*
  • Optic Neuritis / cerebrospinal fluid*
  • Prognosis
  • Severity of Illness Index
  • Young Adult


  • Adipokines
  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Lectins
  • Neurofilament Proteins
  • neurofilament protein L