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Intrathecal chitotriosidase and the outcome of multiple sclerosis

Institute of Clinical Neurology, University of Sassari, Sassari, Italy, stefanos{at}uniss.it

R Barone

Institute of Chemistry and Technology of Polymers, CNR, Catania, Sicily, Italy

G Arru

Institute of Clinical Neurology, University of Sassari, Sassari, Italy

M L Fois

Institute of Clinical Neurology, University of Sassari, Sassari, Italy

M Pugliatti

Institute of Clinical Neurology, University of Sassari, Sassari, Italy

A Sanna

Institute of Clinical Neurology, University of Sassari, Sassari, Italy

G Rosati

Institute of Clinical Neurology, University of Sassari, Sassari, Italy

S Musumeci

Department of Pharmacology, Gynecology-Obstetrics, Pediatrics, University of Sassari and Institute of Population Genetics, CNR, Alghero, Italy

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.

Key Words: cerebrospinal fluid • chitotriosidase • macrophage • multiple sclerosis • prognosis

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