title: Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank samples.
abstract: BACKGROUND
  The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple sclerosis (MS) risk. Interaction between these two factors has been proposed.
  
  
  OBJECTIVE
  The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.
  
  
  METHODS
  Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed.
  
  
  RESULTS
  The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1(402-502), and domain EBNA-1(385-420); p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found.
  
  
  CONCLUSIONS
  We confirm that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Section of Neurology at Umeå University, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Salzer
authors.forename: Maria
authors.initials: M
authors.lastname: Nyström
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Hans
authors.initials: H
authors.lastname: Stenlund
authors.forename: Göran
authors.initials: G
authors.lastname: Wadell
authors.forename: Peter
authors.initials: P
authors.lastname: Sundström
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D011446:Prospective Studies; D012306:Risk; D013548:Sweden; D014015:Tissue Banks; D014807:Vitamin D / Q000032:analysis* / Q000145:classification
chemical_list: D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D014807:Vitamin D
keywords: Epstein-Barr Nuclear Antigen-1 (EBNA-1); Epstein-Barr virus (EBV); Multiple sclerosis; case-control study; risk factors in epidemiology; vitamin D (25(OH)D)