010 – Chitinase 3-like 1 as a biomarker of multiple sclerosis progression
Laura Cubas-Nuñez (1+) – Sara Garcia Gil-Perotin (1, 2+) – Jessica Castillo-Villalba (1) – Raquel Gasque-Rubio (1) – Sara Carratal-Bosc (1) – Carmen Alcal-Vicente (2) – Francisco Prez-Miralles (2) – Hans Lassmann (3) – Bonaventura Casanova-Estruch (1, 2)
Multiple Sclerosis and Neural Regeneration Research Group. Health Research Institute La Fe. Avda. Fernando Abril Martorell, 102. 46026 Valncia (1)
Objective: To analyze the Chitinase-3-like-1 (CHI3L1) pattern of expression in distinct clinical multiple sclerosis (MS) phenotypes and well-defined pathological lesions.
Material and methods: This study was performed on brain autopsy tissue from 21 patients with MS and six age-matched controls collected in the Center for Brain Research of the Medical University of Vienna. Five cases of acute MS (AMS), one of relapsing-remitting MS (RRMS), five with primary progressive MS (PPMS) and ten with secondary progressive MS (SPMS) have been analyzed. Normal appearing white matter (NAWM), slowly expanding lesions (SEL), classical active lesions following pattern I, II or III type of demyelination and inactive lesions were studied. We combined immunohistochemistry and digital optical densitometry (OD) to carry out the study.
Results: CHI3L1 OD was scarce in controls (OD=0,108 (0,045-0,174)), in cortex and NAWM, with only some glial cells stained. Classical active white matter lesions contained high CHI3L1 OD values (6,067 (4,687-6,91)), with a lot of positive glial cells like microglia, macrophages and astrocytes in all MS cases. In cortical lesions, both AMS and progressive MS, the most CHI3L1 was located in neurons, but CHI3L1 OD was higher in progressive forms compared to AMS (0,726 (0,018-1,11) vs 0,342 (0,033-0,677)) and significantly higher compared to the only case of RRMS (OD=0,037). Moreover, CHI3L1 OD in cortex, grouping all MS phenotypes, correlated positively with the disease duration (r=0,593, p=0,026) and, inversely, CHI3L1 OD in NAWM correlated negatively (r=-0,514, p= 0,017).
Conclusion: In inflammatory stages of the disease, CHI3L1 is present mainly in glial cells in active white matter lesions, but when the disease progresses its expression is increased in cortical neurons. These results reinforce the role of CHI3L1 as a biomarker of inflammation in acute phenotypes and disease progression and cortical damage in progressive phenotypes.