Wide Cytokine Analysis in Cerebrospinal Fluid at Diagnosis Identified CCL-3 as a Possible Prognostic Factor for Multiple Sclerosis

Abstract

<b>Background:</b> Apart from IgG oligoclonal bands, no other biomarker has, to date, been validated for diagnostic and/or prognostic purposes in multiple sclerosis (MS). <b>Aim:</b> To investigate a wide panel of cytokines and chemokines in the cerebrospinal fluid (CSF) of relapsing-remitting MS (RRMS) patients and evaluate their association with clinical and magnetic resonance imaging (MRI) parameters, as well as their predictive clinical value. <b>Methods:</b> Fifty-one RRMS at clinical onset and 17 other not inflammatory neurological disorders (ONINDs) underwent brain MRI (including 3D-T1, 3D-FLAIR, and 3-DIR sequences) and CSF examination. Eighty-seven cytokines and chemokines were analyzed in CSF by Multiplex technology. <b>Results:</b> Compared to ONIND, CXCL-10, CXCL-11, CXCL-13, CCL-1, CCL-2, CCL-3, CCL-22, IL-16, and BAFF were significantly (<i>p</i> < 0.05) increased in RRMS CSF. However, only CCL-3 was associated with both MS diagnosis and IgGOB detection. Based on a 95%CI in ONIND (cut-off value: 0.798 pg/ml) and ROC analysis (cut-off value: 0.495 pg/ml), RRMS patients were stratified in CCL-3^high (>0.736 pg/mL), CCL-3^medium, and CCL-3^low (<0.495 pg/ml). Survival analysis disclosed a strong association between high CCL-3 values and disease reactivation (OR = 4.9, 95%CI: 1.8-13.3, <i>p</i> < 0.005) in the following 2 years. <b>Conclusions:</b> CCL-3 deserves further investigation as a candidate prognostic biomarker for RRMS.