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

• Published in: Medical microbiology and immunology Vol. 205; no. 2; pp. 143 - 154
• Main Authors: Nejati, Ahmad, Shoja, Zabihollah, Shahmahmoodi, Shohreh, Tafakhori, Abbas, Mollaei-Kandelous, Yaghoub, Rezaei, Farhad, Hamid, Kabir Magaji, Mirshafiey, Abbas, Doosti, Rozita, Sahraian, Mohammad Ali, Mahmoudi, Mahmood, Shokri, Fazel, Emery, Vince, Marashi, Sayed Mahdi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016; Springer Nature B.V
• Subjects: Adult; Antibodies, Viral - immunology; Biomarkers; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Cytokines; Cytokines - metabolism; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - virology; Epstein-Barr Virus Nuclear Antigens - immunology; Female; Humans; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunology; Male; Medical Microbiology; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - complications; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - metabolism; Nervous system; Original Investigation; Viral Load; Virology; Vitamin D; Vitamin D - blood; Vitamin D - metabolism; Young Adult; Relapsing-remitting multiple sclerosis; Immune biomarker signature; Vitamin D; Epstein–Barr virus
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-015-0437-7

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.