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Med Microbiol Immunol. 2016 Apr;205(2):143-54. doi: 10.1007/s00430-015-0437-7. Epub 2015 Sep 13.

EBV and vitamin D status in relapsing-remitting multiple sclerosis patients with a unique cytokine signature.

Author information

1
Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran.
2
Virology Department, Pasteur Institute of Iran, Tehran, Iran.
3
Iranian Centre of Neurological Research, Department of Neurology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
4
Immunology Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
5
Tehran University of Medical Sciences, International Campus (TUMS-IC), Tehran, Iran.
6
Immunology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
7
MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
8
Department of Epidemiology and Biostatistics, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
9
Department of Microbial and Cellular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
10
Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, 14155-6446, Iran. m-marashi@tums.ac.ir.
11
Tehran University of Medical Sciences, International Campus (TUMS-IC), Tehran, Iran. m-marashi@tums.ac.ir.

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.

KEYWORDS:

Epstein–Barr virus; Immune biomarker signature; Relapsing-remitting multiple sclerosis; Vitamin D

PMID:
26365612
DOI:
10.1007/s00430-015-0437-7
[Indexed for MEDLINE]

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