CHI3L1 Protein Levels May Mark Neurologic Disability in PPMS, Study Suggests

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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SERPINA3, PPMS biomarker

Levels of a protein linked to inflammation and neurodegeneration in multiple sclerosis (MS) — called chitinase 3-like-1 (CHI3L1) — may prove to be a cerebrospinal fluid biomarker of neurologic disability in primary progressive MS (PPMS), a pilot study suggests.

Higher CHI3L1 levels at PPMS diagnosis showed a tendency to be associated with greater disability at follow-up, its researchers wrote, although this study was limited in length and sample size, and further work is needed.

The study, “CSF chitinase 3-like-1 association with disability of primary progressive MS,” was published in the journal Neurology.

Studies exploring the prognostic value of proteins found in the cerebrospinal fluid (CSF) have identified CHI3L1, CHI3L2, and neurofilament light chain (NfL) as possible MS biomarkers, as their levels appear to correlate with inflammation and neurodegeneration in these patients. CSF is the clear liquid that circulates in the brain and spinal cord.

“Reported data have also pointed at measuring CHI3L1 and NfL to anticipate conversion to progressive disease, as well as supporting the biomarker use of CHI3L1 to monitor disease activity in secondary progressive MS and response to interferon-beta in relapsing-remitting patients,” THE investigators wrote.

However, the potential utility of these proteins as predictive markers of MS course in people with PPMS is unknown.

To investigate if these three proteins — CHI3L1, CHI3L2, and NfL — could predict PPMS course, researchers in Spain analyzed their levels in CSF samples from 25 adult PPMS patients.

All included patients had been diagnosed with PPMS for 10 or fewer years, and had not used a disease-modifying therapy for at least six months. All had also participated in the Understanding Primary Progressive Multiple Sclerosis (UPPMS) study, a non-interventional study that recruited participants from 11 hospitals in Spain between January and July 2017.

Levels of CSF proteins were measured in samples collected at the time of diagnosis in all patients, through a technique called the enzyme-linked immunosorbent assay (ELISA).

Investigators also reviewed one-year follow-up exams of patients’ disability progression as assessed on the Expanded Disability Status Scale, or EDSS, scores, and cognitive function assessed using Brief Repeatable Neuropsychological Battery tests.

Researchers found that at diagnosis, higher levels of CHI3L1 were associated with higher EDSS scores, reflecting a greater degree of disability. The same association was found at the one-year follow-up.

Conversely, higher levels of CHI3L2 at diagnosis were found to associate with lower EDSS scores, meaning less disability. No significant correlations were seen between CHI3L2 levels at follow-up, and between NfL levels at any time point.

Additional analyses also found that higher CHI3L1 levels were associated with a higher risk of disability progression. Such correlations were not found with the other two CSF proteins.

“This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS,” the investigators wrote.

“These findings warrant further confirmatory assessment in larger samples of patients with PPMS,” they added.

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