Dataset Information

Exploring the effect of vitamin D₃ supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

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.

SUBMITTER: Rolf L

PROVIDER: S-EPMC6108041 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploring the effect of vitamin D<sub>3</sub> supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Rolf Linda L Muris Anne-Hilde AH Mathias Amandine A Du Pasquier Renaud R Koneczny Inga I Disanto Giulio G Kuhle Jens J Ramagopalan Sreeram S Damoiseaux Jan J Smolders Joost J Hupperts Raymond R

Multiple sclerosis (Houndmills, Basingstoke, England) 20170721 10

<h4>Background</h4>Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS).<h4>Objectives</h4>To investigate the effect of high-dose vitamin D<sub>3</sub> 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.<h4>Methods</h4>This study utilized blood samples from ...[more]

PMID: 28731372

Similar Datasets

Project description:BackgroundVitamin D insufficiency is associated with risk of multiple sclerosis (MS) relapse; whether supplementation influences prognosis is unknown. The Vitamin D to Ameliorate MS (VIDAMS) trial aimed to determine if high dose (5000 International Units (IU)/day) versus low dose (600 IU/day) vitamin D3, added to daily glatiramer acetate (GA), reduced the risk of clinical relapse in people with established relapsing remitting MS (RRMS) over 96 weeks.MethodsVIDAMS is a randomised, phase 3, double-blind, multi-centre, controlled trial conducted at sixteen neurology clinics in the United States. Participants with MAGNIMS 2010 RRMS, aged 18-50 years, with recent disease activity were eligible to enroll if they had an Expanded Disability Status Scale score ≤4.0; minimum serum 25-hydroxyvitamin D level of 15 ng/ml within 30 days of screening; and average ≤ 1000 IU supplemental vitamin D3 daily in the 90 days prior to screening. Of 203 screened, 183 were eligible for the 30-day run-in to assess GA adherence, after which 172 were randomised 1:1 to low dose vitamin D3 (LDVD) or high dose vitamin D3 (HDVD), and were followed every 12 weeks for 96 weeks. The primary outcome was the proportion that experienced a confirmed relapse and analyses used Kaplan Meier and Cox proportional hazards models. 165 participants returned for ≥1 follow-up visit and were included in the primary and safety analyses; 140 completed a week 96 visit. This study was registered with ClinicalTrials.gov, NCT01490502.FindingsBetween March 22, 2012 and March 8, 2019, 172 participants were enrolled and randomised (83 LDVD, 89 HDVD) and differed at baseline only in gender and race: more males received HDVD (31%) than LDVD (16%), and fewer Black participants received HDVD (12%) than LDVD (22%). Among 165 participants with at least one follow-up visit, the proportion experiencing confirmed relapse did not differ between LDVD and HDVD [at 96 weeks: 32% vs. 34%, p = 0.60; hazard ratio (HR): 1.17 (0.67, 2.05), p = 0.57]. There was no hypercalcaemia. Three participants developed nephrolithiasis or ureterolithiasis (1 in the LDVD and 2 in the HDVD group). Two were possibly related to study drug; and one was presumed related to concomitant treatment with topiramate for migraine.InterpretationVIDAMS provides evidence that HDVD supplementation, added to GA, does not reduce the risk of clinical relapse in people with RRMS. Taken together with the null findings of previous trials, these results suggest that prescribing higher doses of vitamin D for purposes of modifying the RRMS course may not be beneficial.FundingThis investigation was supported by a grant from the National Multiple Sclerosis Society (RG 4407A2/1). Teva Neuroscience, Inc. provided Copaxone (GA) for the duration of the trial.

Project description:BackgroundCortical, thalamic and hippocampal gray matter atrophy in relapsing-remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied.ObjectiveTo assess MS damage to a hippocampal-thalamic-prefrontal network and the relative contributions of its components to specific cognitive domains.MethodsWe calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity.ResultsRRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory.ConclusionsHippocampal-thalamic-prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

Dataset Information

Exploring the effect of vitamin D₃ supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Background

Objectives

Methods

Results

Conclusion

Publications

Exploring the effect of vitamin D<sub>3</sub> supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Background

Objectives

Methods

Results

Conclusion

Publications

Exploring the effect of vitamin D&lt;sub&gt;3&lt;/sub&gt; supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Exploring the effect of vitamin D₃ supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Exploring the effect of vitamin D<sub>3</sub> supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.