Free Communications 1Friday, October 04, 2013, 09:27 - 09:39
Validation of cerebrospinal fluid chitinase 3-like 1 as a prognostic biomarker of conversion to multiple sclerosis and disease severity in patients with clinically isolated syndromesE. Cantó, M. Tintoré, C. Costa, G. Arrambide, L.M. Villar, J.C. Álvarez-Cermeño, F. Deisenhammer, H. Hegen, M. Khademi, T. Olsson, F. Piehl, A. Bartos, D. Simova, J. Kotoucova, J. Kuhle, L. Kappos, J.A. García-Merino, A. Saiz, Y. Blanco, R. Hintzen, N. Jafari, D. Brassat, H. Tumani, F. Lauda, R. Roesler, K. Rejdak, E. Papuc, C. de Andrés, M. Khalil, D. Galimberti, E. Scarpini, X. Montalban, M. Comabella (Barcelona, Madrid, ES; Innsbruck, AT; Solna, SE; Prague, CZ; Basel, CH; Rotterdam, NL; Toulouse, FR; Ulm, DE; Lublin, PL; Graz, AT; Milan, IT)
Background and Objective: In a previous study conducted by our group in cerebrospinal fluid (CSF) samples from patients with clinically isolated syndromes (CIS), chitinase 3-like 1 (CHI3L1) protein levels were found to be significantly increased in patients who later converted to clinically definite MS (CDMS) compared to patients who remained as CIS, and CHI3L1 levels correlated with disability progression during follow-up. Based on these findings, in the present study we aimed to validate CHI3L1 as a prognostic biomarker associated with conversion to MS and with the development of neurological disability in a large cohort of CIS patients.
Methods: CSF samples from 813 CIS patients (419 who converted to CDMS and 394 who remained as CIS during a mean follow-up (standard deviation) of 5.3 years (3.6)) and 559 controls with other neurological diseases (non-inflammatory – ONIND, n=438; inflammatory – OIND, n=121) were recruited from 15 European MS centres. CSF CHI3L1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Multivariate Cox proportional hazard regression adjusted by number of Barkhof criteria at baseline MRI, presence of oligoclonal bands, and age at CIS onset as covariates was used to evaluate the association between CSF CHI3L1 levels and time to conversion to MS based on Poser and 2005 McDonald criteria, and time to reach EDSS 3.0. CSF protein levels were stratified into high and low according to a cut-off value of 287.9 ng/ml that was obtained by the group in a previous study.
Results: Age-adjusted CSF CHI3L1 levels were significantly higher in CIS patients who converted to CDMS compared to CIS patients who did not convert to CDMS (p=0.004) and controls with ONIND (p=2.4x10^-7). In the Cox regression analysis, CSF CHI3L1 levels were an independent risk factor for time to conversion to MS based on Poser (p=0.001) and McDonald criteria (p=1.8x10^-4), and time to reach EDSS 3.0 (p=8.9x10^-10). CIS patients with high CHI3L1 levels had a significantly shorter time to CDMS compared with patients with low CHI3L1 levels (median time in patients with high and low CSF CHI3L1 levels: 13.0 months versus 54.8 months; log-rank p-value=2.7x10^-7).
Conclusions: CSF CHI3L1 protein levels are an independent risk factor for conversion to MS and more rapid development of disability. Altogether, these findings reinforce the role of CHI3L1 as a prognostic biomarker in patients with CIS.
Authors have nothing to disclose