CHI3L1 Expression in Neutrophils and Plasma of Multiple Sclerosis Patients: Implications for Pathogenesis and a Potential Biomarker

This study investigated the expression and subcellular localization of chitinase-3-like protein 1 (CHI3L1) in neutrophils and plasma from untreated and dimethyl fumarate (DMF)-treated multiple sclerosis (MS) patients, and healthy controls. Intracellular CHI3L1 expression was assessed in CD66b+ neutrophils and CD16+ cells using flow cytometry. Subcellular localization was analyzed by confocal microscopy using markers for various neutrophil granules, while ELISA measured plasma CHI3L1 and lactoferrin levels. We found that both intracellular CHI3L1 levels (expressed as mean fluorescence intensity, MFI) and the proportion of CD66b+ cells were significantly increased in MS patients compared to healthy controls. CHI3L1 was found to colocalize with CD66b+ specific granules. While plasma CHI3L1 levels in untreated MS patients remained comparable to those of healthy controls, a significant increase in both intracellular and plasma CHI3L1 was observed in DMF-treated MS patients. The lack of correlation between plasma lactoferrin and CHI3L1 might suggest selective release mechanisms or differential synthesis of these proteins, despite their common storage in specific granules. These findings highlight the role of neutrophils as a peripheral source of CHI3L1 and suggest a complex association between neutrophil-derived CHI3L1 and the differences observed in DMF-treated MS patients.