title: Increased cortical lesion load and intrathecal inflammation is associated with oligoclonal bands in multiple sclerosis patients: a combined CSF and MRI study.
abstract: Although IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) are a frequent phenomenon in multiple sclerosis (MS) patients, their relationship with grey matter lesions, intrathecal/meningeal inflammation and clinical evolution has not been clarified yet. The aim of our study was to assess the relationship between the OCBs, the inflammatory/neurodegenerative CSF profile at diagnosis, the cortical lesion load and the clinical evolution after 10 years.
  
  
  
  This is a 10-year observational, cross-sectional study based on a combined MRI, cognitive and CSF profiling of the examined patients. Forty consecutive OCB-negative (OCB-) and 50 OCB-positive (OCB+) MS patients were included in this study. Both groups had mean disease duration of 10 years and were age and gender matched. Each patient underwent neurological and neuropsychological evaluation and 3-T MRI. Analysis of the presence and levels of 28 inflammatory mediators was performed in the CSF obtained from 10 OCB- MS, 11 OCB+ MS and 10 patients with other neurological conditions.
  
  
  
  Increased number of CLs was found in OCB+ compared to OCB- patients (p < 0.0001), whereas no difference was found in white matter lesion (WML) load (p = 0.36). The occurrence of OCB was also associated with increased levels of neurofilament light chains and of several inflammatory mediators linked to B lymphocyte activity and lymphoid-neogenesis (CXCL13, CXCL12, CXCL10, TNFSF13, TNFSF13B, IL6, IL10) and other pro-inflammatory molecules, such as IFN-γ, TNF, MMP2, GM-CSF, osteopontin and sCD163. Finally, the occurrence of OCB was found associated with poor prognosis, from both physical and cognitive points of view.
  
  
  
  OCB at MS onset are associated with more severe GM pathology and with a more severe physical disability and cognitive impairment after 10 years. Increased levels of cytokines linked to B cell activation, lymphoid-neogenesis, and pro-inflammatory immune response in the CSF of OCB+ patients support the hypothesis of crucial role played by compartmentalized, intrathecal B cell response in the pathogenesis of CLs and OCB production.
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.|Unit of Neurology, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Farina
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.|Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Magliozzi
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pitteri
authors.affiliation: Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Reynolds
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.|Department EOMM, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gajofatto
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Benedetti
authors.affiliation: Department EOMM, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facchiano
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Monaco
authors.affiliation: Neurology B, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Policlinico "G.B. Rossi" Borgo Roma, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. massimiliano.calabrese@univr.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Calabrese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000134:cerebrospinal fluid* / Q000235:genetics; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000150:complications / Q000000981:diagnostic imaging; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*; D053495:Osteopontin / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D016207:Cytokines; D043025:Oligoclonal Bands; D053495:Osteopontin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020778:Matrix Metalloproteinase 2
keywords: CSF; Cytokines; Grey matter; IgG; MRI; Multiple sclerosis; Neurodegeneration; Neuroinflammation; OCB; Oligoclonal bands