title: Untreated relapsing remitting multiple sclerosis patients show antibody production against latent Epstein Barr Virus (EBV) antigens mainly in the periphery and innate immune IL-8 responses preferentially in the CNS.
abstract: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS). Reliable biomarkers are urgently needed for its diagnosis and management, and as clues to its pathogenesis, in which EBV is implicated.
  
  
  
  To measure IgG antibodies against EBV nuclear antigen-1 (EBNA-1) and innate inflammation status in paired serum and cerebrospinal fluid (CSF) samples from untreated relapsing-remitting MS (RRMS) patients.
  
  
  
  Anti-EBNA-1 IgG titers and IL-8, IL-1β, IL-6, IL-10, TNF-α and IL-12p70 cytokine levels were measured in 20 untreated RRMS-patients and 17 healthy controls.
  
  
  
  We found higher serum anti-EBNA-1 IgG and IL-8 levels in RRMS-patients than in healthy controls. Interestingly, levels of IL-8 - relative to total protein - were much higher in the CSF, whereas the anti-EBNA-1 antibodies were significantly higher in the sera. More detailed analysis showed that anti-EBNA-1 antibodies relative to total IgG were also higher in the serum in the majority of RRMS patients compared to CSF. Levels of anti-EBNA-1 IgG and IL-8 showed a strong correlation between serum and CSF.
  
  
  
  These findings in newly diagnosed RRMS-patients imply anti-EBNA-1 antibody production mainly in the periphery and innate immune responses preferentially in the CNS. Both their potential as disease biomarkers and their implications for the pathogenesis of MS warrant further investigation.
authors.affiliation: Department of Neuroscience and Trauma, Neuroinflammation and Psychoneuroimmunology Group, Blizard Institute, Queen Mary University London, UK. Electronic address: s.sisay@qmul.ac.uk.
authors.forename: Sofia
authors.initials: S
authors.lastname: Sisay
authors.affiliation: Department of Neuroscience and Trauma, Neuroinflammation and Psychoneuroimmunology Group, Blizard Institute, Queen Mary University London, UK; MS Unit, Department of Neurology, Hospital Clinico San Carlos, IdISSC, Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Lopez-Lozano
authors.affiliation: Department of Neuroscience and Trauma, Neuroinflammation and Psychoneuroimmunology Group, Blizard Institute, Queen Mary University London, UK.
authors.forename: Marius
authors.initials: M
authors.lastname: Mickunas
authors.affiliation: Preventive Medicine Department, Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Quiroga-Fernández
authors.affiliation: Division of Neurology, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: jacqueline.palace@ndcn.ox.ac.uk.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
authors.affiliation: Flow cytometry facility, Blizard Institute, Queen Mary University London, UK. Electronic address: g.warnes@qmul.ac.uk.
authors.forename: Gary
authors.initials: G
authors.lastname: Warnes
authors.affiliation: MS Unit, Department of Neurology, Hospital Clinico San Carlos, IdISSC, Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez-Lafuente
authors.affiliation: Department of Neuroscience and Trauma, Neuroinflammation and Psychoneuroimmunology Group, Blizard Institute, Queen Mary University London, UK. Electronic address: priyamvadadua@hotmail.com.
authors.forename: Priyamvada
authors.initials: P
authors.lastname: Dua
authors.affiliation: Department of Neuroscience and Trauma, Neuroinflammation and Psychoneuroimmunology Group, Blizard Institute, Queen Mary University London, UK. Electronic address: u.meier@qmul.ac.uk.
authors.forename: Ute-Christiane
authors.initials: UC
authors.lastname: Meier
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000276:immunology*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D016207:Cytokines; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D016209:Interleukin-8; C417029:EBV-encoded nuclear antigen 1
keywords: Anti-EBNA-1 antibodies; Cerebrospinal fluid; Epstein-Barr virus; IL-8 cytokine; Innate immune response; Relapsing-remitting multiple sclerosis; Serum