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

Marco Puthenparampil,Francesca Rinaldi,Francesca Grassivaro,Lisa Federle,Paola Perini,Sofia Zywicki,Chiara Cazzola,Maria Pia Sormani,Paolo Gallo,Erica Stropparo,Francesca Bovis

doi:10.3389/fimmu.2020.00174

Marco Puthenparampil, Francesca Rinaldi + Show 9 more

Open Access

https://doi.org/10.3389/fimmu.2020.00174

Copy DOI

Abstract

Background: Apart from IgG oligoclonal bands, no other biomarker has, to date, been validated for diagnostic and/or prognostic purposes in multiple sclerosis (MS).Aim: 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.Methods: 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.Results: Compared to ONIND, CXCL-10, CXCL-11, CXCL-13, CCL-1, CCL-2, CCL-3, CCL-22, IL-16, and BAFF were significantly (p < 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-3high (>0.736 pg/mL), CCL-3medium, and CCL-3low (<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, p < 0.005) in the following 2 years.Conclusions: CCL-3 deserves further investigation as a candidate prognostic biomarker for RRMS.

Highlights

Since the earliest disease phases, multiple sclerosis (MS) brain is characterized by a mix of white and gray matter inflammation and neuroaxonal damage and loss [1, 2]
Only CCL-3 was associated with both MS diagnosis and IgG oligoclonal bands (IgGOB) detection
Based on a 95% confidence interval (95%CI) in other not inflammatory neurological disorders (ONINDs) and ROC analysis, RRMS patients were stratified in CCL-3high (>0.736 pg/mL), CCL-3medium, and CCL-3low (

Summary

Introduction

Since the earliest disease phases, multiple sclerosis (MS) brain is characterized by a mix of white and gray matter inflammation and neuroaxonal damage and loss [1, 2]. Except for IgG oligoclonal bands [5], up to date, no biomarker, among those suggested to hold the potential for predicting disease course in MS, has been validated for clinical purposes. Cytokines and chemokines are the most investigated biomarkers of brain inflammation. These soluble factors, which mainly act in paracrine or autocrine manners, constitute a complex, continuously changing and unpredictable network, mainly characterized by redundancy and pleiotropism [6]. If a possibility exists to detect a potential biomarker of inflammation that can be used for clinical purposes, the ideal condition would be to analyze the largest panel of cytokines/chemokines in the cerebrospinal fluid (CSF) of newly diagnosed and untreated patients. Apart from IgG oligoclonal bands, no other biomarker has, to date, been validated for diagnostic and/or prognostic purposes in multiple sclerosis (MS)

Objectives

Methods

Results

Discussion

Conclusion