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Intrathecal chitotriosidase and the outcome of multiple sclerosis
1Institute of Clinical Neurology, University of Sassari, Sassari, Italy. stefanos@uniss.it
Abstract:
Activated macrophages are major effectors at all stages of lesion formation in multiple sclerosis (MS) brain. Here, we report that the macrophage enzyme chitotriosidase (Chit) is significantly elevated both in plasma and cerebrospinal fluid (CSF) of patients with MS as compared to healthy controls and other neurological patients (P<0.001). Furthermore, the Chit activity in blood significantly associates with the MS clinical course (higher in secondary progressive relative to relapsing-remitting, P=0.01) and the clinical severity as measured by Kurtkze's Expanded Disability Status Scale (P<0.001). Also, we found that Chit activity is compartmentalized in the central nervous system of early MS patients and that its CSF/plasma quotient, in the presence of a preserved albumin quotient, correlates with the extent of future clinical deterioration (r=0.91; P<0.001). These findings confirm that innate immunity, here represented by Chit, is clinically relevant in MS and allows, if confirmed, reconsidering novel MS therapeutic strategies specifically aimed at this branch of the immune response.
Insights
Chitotriosidase (Chit) enzyme activity is elevated in multiple sclerosis (MS) patients. Higher Chit levels correlate with MS progression and severity, suggesting innate immunity
Area of Science:
- Neuroimmunology
- Biochemistry
- Clinical Neurology
Background:
- Activated macrophages are key players in multiple sclerosis (MS) lesion development.
- The enzyme chitotriosidase (Chit) is produced by macrophages.
Purpose of the Study:
- To investigate chitotriosidase (Chit) activity in multiple sclerosis (MS) patients.
- To determine the association between Chit activity and MS clinical course and severity.
Main Methods:
- Measured chitotriosidase (Chit) activity in plasma and cerebrospinal fluid (CSF) of MS patients and controls.
- Correlated Chit activity with clinical data, including MS type and Expanded Disability Status Scale (EDSS).
Main Results:
- Chit activity was significantly higher in MS patients compared to controls.
- Elevated Chit levels were associated with progressive MS and higher EDSS scores.
- CSF/plasma Chit quotient correlated with future clinical deterioration in early MS.
Conclusions:
- Innate immunity, represented by Chit, plays a clinically relevant role in multiple sclerosis (MS).
- Chit activity serves as a potential biomarker for MS progression and severity.
- These findings may inform novel therapeutic strategies targeting innate immunity in MS.
