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

Linda Rolf; Anne Hilde Muris; Amandine Mathias; Renaud Du Pasquier; Inga Koneczny; Giulio Disanto; Jens Kuhle; Sreeram Ramagopalan; Jan Damoiseaux; Joost Smolders; Raymond Hupperts

doi:10.1177/1352458517722646

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

Linda Rolf^*, Anne Hilde Muris, Amandine Mathias, Renaud Du Pasquier, Inga Koneczny, Giulio Disanto, Jens Kuhle, Sreeram Ramagopalan, Jan Damoiseaux, Joost Smolders, Raymond Hupperts

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1280-1287
Number of pages	8
Journal	Multiple Sclerosis Journal
Volume	24
Issue number	10
DOIs	https://doi.org/10.1177/1352458517722646
Publication status	Published - 1 Sept 2018
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to the patients for their participation. Also, we thank Stefan Neys, Yassin Jabri, Ruud Theunissen, Inge van Loo; S. Frequin (St. Antonius Hospital, Nieuwegein, the Netherlands), F. Verheul (Groene Hart Hospital, Gouda, the Netherlands), and J. Samijn (Maasstad Hospital, Rotterdam, the Netherlands); and the MS nurses of the participating centers for their contributions to the study. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SOLARIUM study was supported by Merck and Nationaal MS Fonds Nederland.

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SOLARIUM study was supported by Merck and Nationaal MS Fonds Nederland.

Publisher Copyright:
© The Author(s), 2017.

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Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosisFinal published version, 250 KBLicence: CC BY-NC

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Rolf, L., Muris, A. H., Mathias, A., Du Pasquier, R., Koneczny, I., Disanto, G., Kuhle, J., Ramagopalan, S., Damoiseaux, J., Smolders, J., & Hupperts, R. (2018). Exploring the effect of vitamin D₃ supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis. Multiple Sclerosis Journal, 24(10), 1280-1287. https://doi.org/10.1177/1352458517722646

@article{f294b0febaa245a786e7600ae47a6b18,

title = "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.",

author = "Linda Rolf and Muris, {Anne Hilde} and Amandine Mathias and {Du Pasquier}, Renaud and Inga Koneczny and Giulio Disanto and Jens Kuhle and Sreeram Ramagopalan and Jan Damoiseaux and Joost Smolders and Raymond Hupperts",

note = "Funding Information: We are grateful to the patients for their participation. Also, we thank Stefan Neys, Yassin Jabri, Ruud Theunissen, Inge van Loo; S. Frequin (St. Antonius Hospital, Nieuwegein, the Netherlands), F. Verheul (Groene Hart Hospital, Gouda, the Netherlands), and J. Samijn (Maasstad Hospital, Rotterdam, the Netherlands); and the MS nurses of the participating centers for their contributions to the study. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SOLARIUM study was supported by Merck and Nationaal MS Fonds Nederland. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SOLARIUM study was supported by Merck and Nationaal MS Fonds Nederland. Publisher Copyright: {\textcopyright} The Author(s), 2017.",

year = "2018",

month = sep,

day = "1",

doi = "10.1177/1352458517722646",

language = "English",

volume = "24",

pages = "1280--1287",

journal = "Multiple Sclerosis Journal",

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Rolf, L, Muris, AH, Mathias, A, Du Pasquier, R, Koneczny, I, Disanto, G, Kuhle, J, Ramagopalan, S, Damoiseaux, J, Smolders, J & Hupperts, R 2018, 'Exploring the effect of vitamin D₃ supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis', Multiple Sclerosis Journal, vol. 24, no. 10, pp. 1280-1287. https://doi.org/10.1177/1352458517722646

TY - JOUR

T1 - Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis

AU - Rolf, Linda

AU - Muris, Anne Hilde

AU - Mathias, Amandine

AU - Du Pasquier, Renaud

AU - Koneczny, Inga

AU - Disanto, Giulio

AU - Kuhle, Jens

AU - Ramagopalan, Sreeram

AU - Damoiseaux, Jan

AU - Smolders, Joost

AU - Hupperts, Raymond

N1 - Funding Information: We are grateful to the patients for their participation. Also, we thank Stefan Neys, Yassin Jabri, Ruud Theunissen, Inge van Loo; S. Frequin (St. Antonius Hospital, Nieuwegein, the Netherlands), F. Verheul (Groene Hart Hospital, Gouda, the Netherlands), and J. Samijn (Maasstad Hospital, Rotterdam, the Netherlands); and the MS nurses of the participating centers for their contributions to the study. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SOLARIUM study was supported by Merck and Nationaal MS Fonds Nederland. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SOLARIUM study was supported by Merck and Nationaal MS Fonds Nederland. Publisher Copyright: © The Author(s), 2017.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

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U2 - 10.1177/1352458517722646

DO - 10.1177/1352458517722646

M3 - Article

C2 - 28731372

AN - SCOPUS:85043400021

SN - 1352-4585

VL - 24

SP - 1280

EP - 1287

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 10

ER -

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

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