Tear CHI3L1 in multiple sclerosis: a non-invasive biomarker linked to disease progression

To evaluate tear CHI3L1 (tCHI3L1) as a minimally invasive biomarker in multiple sclerosis (MS), compare it with serum and cerebrospinal fluid (CSF) CHI3L1, and assess associations with clinical phenotype and disease measures.

This cross-sectional study included 111 MS patients (71 relapsing-remitting MS [RRMS] and 40 progressive MS [PMS]) and 23 healthy controls (HC). tCHI3L1 was quantified by optimized ELISA and normalized to tear volume (tCHI3L1 ratio). Paired tear-serum samples were available for 99 patients to measure sCHI3L1, sGFAP, and sNFL. Associations with age, Expanded Disability Status Scale (EDSS), and disease duration, were analyzed. An independent cohort of 34 patients with paired tear-serum-CSF samples was used to assess biomarker relationships across biological fluids. Receiver operating characteristic analyses evaluated discrimination between PMS and RRMS.

PMS patients showed higher tCHI3L1 ratios than RRMS patients (p = 0.033) and HC (p = 0.024). Tear and serum CHI3L1 levels were not correlated. In patients with matched tear-serum-CSF samples, the tCHI3L1 ratio showed a trend toward correlation with CSF CHI3L1 (r = 0.3; p = 0.08), becoming significant in patients without inflammatory activity (r = 0.45; p = 0.038). Serum biomarkers correlated with age, disease duration, and EDSS. sNFL, followed by sGFAP, showed the best discrimination between PMS and RRMS, whereas serum and tear CHI3L1 showed the lowest discriminatory power.

tCHI3L1 is elevated in PMS and may provide complementary information on compartment-specific disease biology. Its minimally invasive nature supports further evaluation as an accessible biomarker in MS.