Effect of high-dose vitamin D3supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis.
BACKGROUND
Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology.


OBJECTIVE
To examine effects of high-dose oral vitamin D3supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS.


METHODS
Serum 25-hydroxyvitamin D3(25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3supplementation (20,000 IU/week) (NCT00785473).


RESULTS
The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3supplementation did not affect antibodies against VCA, CMV or VZV.


CONCLUSIONS
The results indicate that high-dose oral vitamin D3supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.
Department of Neurology, Akershus University Hospital, Lørenskog, Norway/Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Egil
E
Røsjø
Institute of Clinical Medicine, University of Oslo, Oslo, Norway/Department of Immunology and Transfusion Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Andreas
A
Lossius
Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Nada
N
Abdelmagid
Institute of Clinical Medicine, University of Oslo, Oslo, Norway/Helse Øst Health Services Research Centre, Akershus University Hospital, Lørenskog, Norway.
Jonas C
JC
Lindstrøm
Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
Margitta T
MT
Kampman
Department of Health and Care Sciences, University of Tromsø, Tromsø, Norway/Department of Clinical Therapeutic Services, University Hospital of North Norway, Tromsø, Norway.
Lone
L
Jørgensen
Department of Pharmacology and Clinical Neuroscience, Section of Neurology, Umeå University, Umeå, Sweden.
Peter
P
Sundström
Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Tomas
T
Olsson
Department of Neurology, University Hospital of North Norway, Tromsø, Norway/Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Linn H
LH
Steffensen
KG Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen, Norway/Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Øivind
Ø
Torkildsen
Department of Neurology, Akershus University Hospital, Lørenskog, Norway/Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Trygve
T
Holmøy
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002762:Cholecalciferol / Q000627:therapeutic use*; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood; D005260:Female; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D055815:Young Adult
D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D002762:Cholecalciferol; C417029:EBV-encoded nuclear antigen 1
EBV antibodies; Relapsing-remitting multiple sclerosis; vitamin D