title: EBV & HHV6 reactivation is infrequent and not associated with MS clinical course.
abstract: BACKGROUND
  Among the environmental factors associated with multiple sclerosis (MS) causation, some of the strongest associations are with Epstein-Barr virus (EBV), and to a lesser extent human herpesvirus 6 (HHV6). Associations with clinical course are less conclusive, however.
  
  
  METHODS
  We evaluated serum anti-EBV-EA-R IgG and anti-HHV6 IgM, and EBV and HHV6 viral load (VL) for their associations with relapse, disability, and progression in disability in a prospective cohort of 198 participants with clinically definite MS.
  
  
  RESULTS
  Anti-EBV-EA-R IgG was detected in 81.8% of cases at study entry, and titers remained essentially unchanged during the study. Anti-HHV6 IgM was detected in only one participant, and EBV-VL (29%) and HHV6-VL (1.8%) were detected in a minority of samples, and where detected levels were low. Our previously demonstrated association between anti-HHV6 IgG and relapse hazard was not affected by adjustment for parameters of reactivation. We found no evidence that any of the viral markers were associated with disability or progression in disability. In relation to relapse, only EBV-VL was positively associated, although this was strongly influenced by a single individual.
  
  
  CONCLUSIONS
  Using a prospective cohort design, we found no convincing evidence that reactivation parameters of EBV or HHV6 were associated with subsequent MS relapse hazard or progression in disability, confirming previous findings, and indicating that herpesvirus reactivation is not an important driver of relapse or disability in this established MS population.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tas., Australia.
authors.forename: S
authors.initials: S
authors.lastname: Simpson
authors.forename: B
authors.initials: B
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Burrows
authors.forename: S
authors.initials: S
authors.lastname: Burrows
authors.forename: D E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: A-L
authors.initials: AL
authors.lastname: Ponsonby
authors.forename: L
authors.initials: L
authors.lastname: Blizzard
authors.forename: T
authors.initials: T
authors.lastname: Dwyer
authors.forename: F
authors.initials: F
authors.lastname: Pittas
authors.forename: I
authors.initials: I
authors.lastname: van der Mei
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000821:virology*; D011446:Prospective Studies; D012008:Recurrence; D019349:Roseolovirus Infections / Q000150:complications*; D019562:Viral Load; D014775:Virus Activation / Q000502:physiology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G
keywords: Epstein-Barr virus; disability; human herpesvirus 6; progression; relapse