Chitinase 3-like 1 plasma levels are increased in patients with progressive forms of multiple sclerosis

Background: Chitinase 3-like 1 (CHI3L1) is upregulated in a wide variety of inflammatory conditions. Recent studies have pointed to a role of CHI3L1 in multiple sclerosis (MS) pathogenesis. Objective: The objective of this study was to investigate the role of plasma CHI3L1 in MS clinical course and disease activity and to evaluate the effect of interferon-beta (IFN beta) treatment on protein levels. Methods: Plasma CHI3L1 levels were determined by ELISA in 57 healthy controls (HC), 220 untreated MS patients [66 primary progressive MS patients (PPMS), 30 secondary progressive MS patients (SPMS), and 124 relapsing-remitting MS patients (RRMS), 94 during clinical remission and 30 during relapse], and 32 MS patients receiving IFN beta treatment. A polymorphism of the CHI3L1 gene, rs4950928, was genotyped in 3274 MS patients and 3483 HC. Results: Plasma CHI3L1 levels were significantly increased in patients with progressive forms of MS compared with RRMS patients and HC. CHI3L1 levels were similar between RRMS patients in relapse and remission. A trend towards decreased CHI3L1 levels was observed in IFN beta-treated patients. Allele C of rs4950928 was significantly associated with PPMS patients and with higher plasma CHI3L1 levels. Conclusions: These findings point to a role of CHI3L1 in patients with progressive forms of MS, particularly in those with PPMS.