title: EBV and vitamin D status in relapsing-remitting multiple sclerosis patients with a unique cytokine signature.
abstract: Multiple sclerosis, a debilitating autoimmune and inflammatory disease of the central nervous system, is associated with both infectious and non-infectious factors. We investigated the role of EBV infection, vitamin D level, and cytokine signature in MS patients. Molecular and serological assays were used to investigate immune biomarkers, vitamin D level, and EBV status in 83 patients with relapsing-remitting multiple sclerosis and 62 healthy controls. In total, 98.8 % of MS patients showed a history of EBV exposure compared to 88.6 % in the healthy group (p = 0.005). EBV DNA load was significantly higher in MS patients than healthy subjects (p < 0.0001). Using a panel of biomarkers, we found a distinct transcriptional signature in MS patients compared to the healthy group with mRNA levels of CD73, IL-6, IL-23, IFN-γ, TNF-α, IL-15, IL-28, and IL-17 significantly elevated in MS patients (p < 0.0001). In contrast, the mRNA levels for TGF-β, IDO, S1PR1, IL-10, and CCL-3 were significantly lower in MS patients compared to healthy controls (p < 0.0001). No significant differences were found with the mRNA levels of IL-13, CCL-5, and FOXP3. Interestingly, in MS patients we found an inverse correlation between vitamin D concentration and EBV load, but not EBNA-1 IgG antibody levels. Our data highlight biomarker correlates in MS patients together with a complex interplay between EBV replication and vitamin D levels.
authors.affiliation: Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Nejati
authors.affiliation: Virology Department, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Zabihollah
authors.initials: Z
authors.lastname: Shoja
authors.affiliation: Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Shahmahmoodi
authors.affiliation: Iranian Centre of Neurological Research, Department of Neurology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Tafakhori
authors.affiliation: Immunology Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Mollaei-Kandelous
authors.affiliation: Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Rezaei
authors.affiliation: Tehran University of Medical Sciences, International Campus (TUMS-IC), Tehran, Iran.
authors.forename: Kabir Magaji
authors.initials: KM
authors.lastname: Hamid
authors.affiliation: Immunology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiey
authors.affiliation: MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Rozita
authors.initials: R
authors.lastname: Doosti
authors.affiliation: MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Sahraian
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Immunology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
authors.affiliation: Department of Microbial and Cellular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
authors.forename: Vince
authors.initials: V
authors.lastname: Emery
authors.affiliation: Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran. m-marashi@tums.ac.ir.|Tehran University of Medical Sciences, International Campus (TUMS-IC), Tehran, Iran. m-marashi@tums.ac.ir.
authors.forename: Sayed Mahdi
authors.initials: SM
authors.lastname: Marashi
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D019562:Viral Load; D014807:Vitamin D / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D016207:Cytokines; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D014807:Vitamin D; C417029:EBV-encoded nuclear antigen 1
keywords: Epstein–Barr virus; Immune biomarker signature; Relapsing-remitting multiple sclerosis; Vitamin D