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Randomized Controlled Trial
. 2018 Sep;24(10):1280-1287.
doi: 10.1177/1352458517722646. Epub 2017 Jul 21.

Exploring the Effect of Vitamin D 3 Supplementation on the anti-EBV Antibody Response in Relapsing-Remitting Multiple Sclerosis

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Free PMC article
Randomized Controlled Trial

Exploring the Effect of Vitamin D 3 Supplementation on the anti-EBV Antibody Response in Relapsing-Remitting Multiple Sclerosis

Linda Rolf et al. Mult Scler. .
Free PMC article

Abstract

Background: Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS).

Objectives: To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels.

Methods: This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored.

Results: The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures.

Conclusion: High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism.

Keywords: Antibodies; EBNA-1; Epstein–Barr virus; multiple sclerosis; supplementation; vitamin D.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.R., A.-H.M., A.M., I.K., G.D., and J.D. report no disclosures. R.D.P. has served on scientific advisory boards and/or received funding for travel or speaker honoraria from Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. J.K.’s institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Genzyme, Novartis, Protagen AG, Roche, and Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, and Genzyme; travel expenses from Genzyme, Merck, Novartis, and Roche; and grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation, Bayer AG, Biogen, Genzyme, Merck, Novartis, and Roche. S.R. was a full-time employee at Evidera at the time of this study. J.S. received lecture and/or consultancy fees from Biogen, Merck, Sanofi-Genzyme, and Novartis. R.H. received honoraria for lectures and advisory boards and Research Grants from Merck, Biogen, Sanofi-Genzyme, Novartis, and Teva.

Figures

Figure 1.
Figure 1.
Anti-EBNA-1 IgG levels of patients with RRMS before and after treatment. (a) Within-group comparisons at T0 and T1 in the placebo group (n = 23), (b) within-group comparisons at T0 and T1 in the vitamin D3 group (n = 30), and (c) between-group comparisons of the anti-EBNA-1 IgG level differences between T1 and T0. Gray lines indicate the medians with interquartile ranges. T0: baseline; T1: week 48.
Figure 2.
Figure 2.
EBV-specific CD8+ T cells of patients with RRMS before and after treatment. ELISPOT assays were performed to detect activated EBV-specific CD8+ T cells secreting interferon-γ. Peripheral blood mononuclear cells (PBMC) of the patients with RRMS were thawed and cultured at 1–2 × 105 cells per well in the presence of pools of CD8-restricted EBV peptides at a concentration of 1 mg/mL. The amount of activated cells is represented by SFC/106 PBMC. (a) Within-group comparisons at T0 and T1 in the placebo group (n = 9), (b) within-group comparisons at T0 and T1 in the vitamin D3 group (n = 11), and (c) between-group comparisons of the differences in SFC/106 PBMC between T1 and T0. Gray lines indicate the medians with interquartile ranges. EBV: Epstein–Barr virus; T0: baseline; T1: week 48; SFC: spot-forming cells.

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