title: Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis.
abstract: BACKGROUND
  Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however.
  
  
  METHODS
  Prospective cohort of 198 persons with clinically definite MS, followed 2002-5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein-Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression.
  
  
  RESULTS
  For the 145 persons with relapsing-remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend (p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males.
  
  
  CONCLUSIONS
  These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing-remitting MS clinical course.
authors.affiliation: 1Menzies Research Institute Tasmania, University of Tasmania, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Simpson
authors.forename: Bruce
authors.initials: B
authors.lastname: Taylor
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Janette
authors.initials: J
authors.lastname: Taylor
authors.forename: Leigh
authors.initials: L
authors.lastname: Blizzard
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.forename: Fotini
authors.initials: F
authors.lastname: Pittas
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.forename: Ingrid
authors.initials: I
authors.lastname: van der Mei
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D036022:Capsid Proteins / Q000276:immunology; D004185:Disability Evaluation; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013648:Tasmania; D013997:Time Factors; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D036022:Capsid Proteins