Chitinase-3-like 1 (CHI3L1) is a glycoprotein produced by monocytes, microglia and activated astrocytes that has been proposed as a diagnostic and prognostic biomarker of progression in MS. A recent meta-analysis of 20 studies reported that CHI3L1 levels in CSF were strongly correlated with the clinical course (Floro et al. Neurol Neuroimmunol Neuroinflamm 2022;9:e1164). Levels were higher in converting clinically isolated syndrome (CIS) vs. non-converting CIS; in MS vs. CIS or healthy controls; and in PPMS vs. RRMS.

In radiologically isolated syndrome (RIS), CHI3L1 was correlated with positive CSF but was not an independent predictor of conversion to RRMS (Thouvenot et al. Mult Scler 2019;25:669-677). The only predictor in that study was the presence of spinal cord lesions. However, other studies have shown that CHI3L1 is associated with spinal cord atrophy in RIS (Schneider et al. Neurol Neuroimmunol Neuroinflamm 2020;8:e906), and with the formation of paramagnetic rim lesions (PRLs) in CIS (Comabella et al. Mult Scler 2022;28:71-81). Interestingly, PRLs were not associated with glial fibrillary acidic protein (GFAP) in serum or CSF, suggesting that CHI3L1 and GFAP reflect somewhat different aspects of MS pathophysiology.

CHI3L1 can provide complementary information to serum neurofilament-light chain levels. In a study of 157 RRMS and PMS patients, RRMS patients commonly presented with elevated NfL and low CHI3L1 levels (Gil-Perotin et al. Front Neurol 2019;10:1008). Increasing levels of both biomarkers heralded the onset of progressive disease. CHI3L1 was a predictor of a 1-point worsening of the EDSS score. The association of CHI3L1 with progressive biology may enable its use as a laboratory test for progression independent of relapse activity (PIRA).